Pharmaceutical Abstracts

\'oL.XIII, No. 1

1947

JANUARY,

PHARMACEUTICAL ABSTRACTS Published by the American Pharmaceutical Association 2215 Constitution Ave., Washington, D. C.

EDITOR:JUSTIN L. POWERS, 2215 Constitution Ave., Washington, D. C.

ABSTRACTORS WILLIAMB. BAKER BETTIEM. BROOKS HENRYM. BURLAGE R. BYRUM WOODROW E. L. CATALINE ZADAM. COPPER AMELIAC. DEDOMINICIS

MELVINF. W. DUNKER S. GITTINGER GEORGIANA SAWEL W. GOLDSTEIN MELVINW. GREEN WILLIAMH. HUNT K ~ L.LKAUPMAN CLIFFORD S. LEONARD NATHAN LEVIN

Modern Remedies :

E. MEYBR A. PAPINEAU-COUTURE

ARTHUR

E. SCHWARTINC FRANKJ. SLAMA

ARTHUR

W. TAYLOR SUMERFORD ELMERH. WIRTH LEE WORRELL

Fixed Oils, Fats, and Waxes.

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Specialties. . . . . . . . . . . . . . . . . . .

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Other Plant Principles. . . . . .

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Synthetics . . . . . . . . . . . . . . . . . . .

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Unclassified . . . . . . . . . . . . . . . .

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Bacteriology . . . . . . . . . . . . . . . . . . .

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Biochemistry . . . . . . . . . . . . . . . . .

Chemistry : General and Physical.. ........

Analytical. . . . . . . . . . . . . . . . . . . 10

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Pharmacognosy Vegetable Drugs.. . . . . . . . . . . . . 26

Organic : Alkaloids., . . . . . . . . . . . . . . . .

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Essential Oils and Related Products. . . . . . . . . . . . . . . .

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Pharmacology, Toxicology, and Therapeutics : Pharmacology.. . . . . . . . . . . . . . . 27

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MODERN REMEDIES SPECIALTIES Pentamidme Isethionate. (May & Baker, Ltd.) is one of the least toxic of the aromatic diamidine compounds. It is a valuable chemotherapeutic agent in the treatment of early cases of Tr#anosomu ganzbknse infection and in kala-azar. I t also promis? to be of value in the prophylaxis of trypanosomiasis. It is available in the form of a 10% solution Chemist, 17 for intramuscular injection.-Retail (A. C. Dell.) (No. 6),30(1946). Sketofax (Burroughs Wellcome and Company) is a liquid insect repellent which is claimed t o set an entirely new standard of efficiency in personal protection against gnats, mosquitoes, and similar pests. I t is a clear, faintly perfumed liquid, issued in capsules containing sufficient liquid for one application t o the face, neck, and other exposed parts. The capsules are packed in attractive cartons of 12 and in boxes of 6 doz. Also available in screw-capped Chemist, jars is the cream insect repellent.-Retail (A. C. DeD.) 17 (No. 6), 15(1946). Solaresenox (The Ethical Division of Nicholas Pty Ltd.) is specifically designed for the treatment by intravenous injection of spirochete infections, including syphilis, yaws, bronchial spirochetosis, and Vincent’s infection. The active principle of “Solarsenox,” arsenoxide sulfate, is mixed with sucrose and sodium bicarbonate. The whole, when dissolved in distilled water, provides a neutral isotonic solution of arsenoxide, a drug which has enjoyed the confidence of the medical profession, both hereandoverseas, for thelast decade. It is marketed in ampuls containing 0.04 Gm. and 0.06 Gm. of the drug. Ampuls containing 10 cc. of sterile doubledistilled water are also available if required.Australasian J. Phurm., 27, 142(1946). (A. C. DeD.) Sulfaguanidme Tabloid (Burroughs Wellcome & Company (Australia) Ltd.) is a sulfanilamide dcrivative. It is specific in the treatment of bacillary dysentery of all types and in carrier cases; also effective in many cases of nonspecific diarrhea, and in neonatal gastro-enteritis. Successful results have been reported also in proctitis of lympogranuloma inguinaole, ulcerative colitis, regional ileitis, and diverticulitis. The drug has been widcly used as a prophylactic measure in surgery of the large intestine “Tabloid” sulfaguanidine is administered orally, i t is available in bottles of 100 and 500.--Australas~n J. Pharm.,27,216(1946). (A. C. DeD.) SynepMcol (Frederick Stearns and Co.) is a new and complete cough treatment containing NeoSynephrine Hydrochloride. It offers a complete cough treatment, as i t combines a sedative (Codeine Phosphate) with dependable expectorants and NeoSynephrine as a bronchodilator. It is packed in 3 sizes: 4 oz., 16 oz.. and 80 02.-Australesian J. Pharm., 27, 141(1946). (A. C. DeD.) Vasano (British Schering, Ltd.) is a new preparation recommended for the prophylaxis and cure of travel sickness, whether the r e u l t of journeying by car, air, train, sea, or any kind of vchiclc likely to cause sickness. It consists of the caniphoric acid salts of the mandragora alkaloids and the claims that are made for it are based upon a large number

of exhaustive scientific experiments and tests which have proved it as an excellent prophylactic against all types of travel sickness. Vasano should be taken about 1hr. before the cause of sickness is likely to be encountered, 2 tablets being a sufficient dose in a majority of cases to prevent an attack. Persons very liable t o travel sickness should take a further dose of 1 tablet aftcr 4 to 6 hr., repeating this dose again after a similar interval. The maximum is 4 tablets in 24 hr. Children under 14 yr. of age may be givcii 1 tablet. If the prophylactic dose of Vasano has been omitted and sickness sets in, this may be relieved by the use of Vasano suppositories. Four is the maximum t o be used in 24 hr. Packings are issued holding 4 and 10 tablets, the suppositories being made available in boxes containing 10 in each. --Refail Cheniist, 17 (No. 4). 30(1946). (A. C. DeD.)

SYNTHETICS Privine is 2-(naphthyl-l-methyl)-imidazolinehydrochloride. I t is a white crystalline substance having m. p. 259” to 260°, soluble in water to about 1070, It is a powerful synthetic vasoconstrictor causing dccongestion of the nasal mucous membrane. I t is recommcnded for the treatment of rhinitis. sinusitis, and hay-fever. Privine is supplied as a 1 : l O O O and 1:2000 solution t o be used as drops. One t o 3 drops instilled in each nostril every 2 t o 6 hr. will suffice in the majority of cases. The half strength solution only should be used for children and nasal packs. Treatment should not be continued for more than 4 to 5 days at a time. Privine, full strength and half strength, is supplied in bottles of fl. oz and 4 fl. OZ.-ANON. Quart. J. Pharm. Phurmacol., 19, 88(1946). (S. W. G.) Sterosan and Its Use. Sterosan, a new antiseptic recently marketed by J. R. Geigy is 5,7-dichloro-8hydroxyquinaldine

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OH This substance is related to Vioform (iodochlorohydroxyquinoline) first marketed by Ciba in 1897 Sterosan is claimed t o be the most active of the hydroxyquinoline derivatives in in vitro tests against cocci (Staphylococci, Streptococci, and Enterococci). Sterosan is being marketed as a 5y0 ointment and THOMANN. Schweiz. as a dusting powder.-J. (M. F. W. D.) [email protected]., 83, 197-98(1945). Sulfamerazine (Nicholas). The Ethical Division of Nicholas Pty. Ltd. announces the release of Sulfamerazine (Nicholas) in bottles of 25, 100, and 500 tablets, a t 5/,17/6, and 82/6 each, wholesale, respectivcly. Each tablet contains 0.5 Gm. (7.7 gr.7 of 2sirlfanilaniido-4-methyl-pyridniidine (sulfamerazine) -Australasian J. Pharm., 57, 27(1946). (A. C. DeD.)

BACTERIOLOGY Air Sterilization. The author reviews briefly ultraviolet irradiation of classroolns, thc use of minute anlourlts of triethylene glycol and propylene glycol, and the effect of oiling floors and bedclothes in keeping air-borne infection at a minimum.-

~XELSONR. h-rms. Arrh. Pcdinlrirs, 63, 266-78 (1936). (M. W. G.)

Bisphenols a s Mildew Preventives on Cotton Fabrics-Fungicidal Activity of. In a series of bisphenols, substitution of C1 or Br in positions para t o

CHEMISTRY

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Rinderpest: the Preparation of Tissue and Egg the OH increased the fungicidal action. A number of compounds were studied but none found t o be Vaccines. A special part of the April issues of thc more active than 2,2-methylenebis-( 4-chlorophenol) Amcruan Journal of Veterinary Research, Part 2, on fabrics. Methods for testing fabric mildew pre- is a series of manuscripts on rinderpest. It is pubventives are discussed.-PAn B. MARSH and lished by an arrangement with the Joint United MARYL. BUTLER. Id. Eng. Chem.. I d . Ed.,38, States-Canadian Commission and Chemical Warfare Service of the U. S. Army whose purpose was to,pro701-5( 1946). (M. W. G.) Cationic Detergents-Protection of Dry Bacteria tect North American livestock against a foreign by Fat Against. The adsorption of quaternary am- plague. Tests were carried out on an island in the St. monium compounds on cell surfaces has been proved Lawrence River and the major projects covered: (1) experimentally. The formation, on hands, of a film the preparation of a tissue vaccine t o quickly surof cationic detergent of which only the outside is- round an epizditic, should it occur, with a ring of germicidal, has been explained as due to an oriented immunized animals, (2) to investigate a means of absorption of the detergents on an organophiic preparing a vaccine more economically by the use of AUTHORS. base such as fat or paraffin.-Ono WN.Proc. embryonated hen’s eggs.-NumRous Am. J . Vet. Research, 7 (No. 23, Part 2), 133-237 SOL Exptl. Biol. Med., 62, 2(1946). (A. E. M.) (M. W. G.) Culture Medium from Groundnut Meal. Ground- (1946). nut meal when digested with papain and augmented Scrub-Typhus-Laboratory Infection with. Four with a trace of liver is a suitable medium for culti- cases of accidental laboratory infection with scrubvating organisms like pneumococcus, the strepto- typhus are reported. Their Occurrence in relation cocci, and the meningococcus.-A. N. SEN,S. SEN t o precautionary measures taken in the laboratory is GUPTA,and U. P. BASU. Indian Med. Gus., 81,75discussed: From two cases the casual rickettsia was 76( 1946). (W. T. S.) isolated in mice and guinea-pigs by intraperitoneal Influenza B in Australia. An epidemic predomi- inoculation. In one of them isolation succeeded nantly of influenza B but including a considerable also in mice which received ground blood-clot intraproportion of influenza A cases, and particularly in- nasally. Th6 diagnosis could be established by Provolving schools and country districts, occurred in teus OXK agglutination tests and complement Victoria in October, 1946. Virus was readily iso- fixation with formolized scrub-typhus antigen. All lated from throat washings by the inoculation of un- the patients had previously received immunizing filtered material plus penicillin and soluble sulfon- injections of scrub-typhus vaccine prepared from amide into the amniotic cavities of chick embryos.cotton-rats. Their complete recovery suggests that F. M. BURNET,J. D. STONE,and S. G. ANDERSON. the vaccine had some protective value.-M. VAN (W. H. H.) Lance:, 250, 807( 1946). DEN ENDE,ct al. Lancet, 251, 4( 1946). Levans-Serological Reactions of, Formed from (W. H. H.) Sucrose and Raflinose by Certain Bacilli. Levans Streptomycin-Bactericidal Action of. Streptoare water-soluble polysaccharides of fructose anhydride synthesized from sucrose and raffinose by mycin is bactericidal for both multiplying and nonsome bacilli. It was found that levans were fQrmed multiplying cultures of K. pneumoniae but not for in sucrose and raflinose broth by B. subtilis, B. fmnis, washed spores of Bacillus sp. 290. Organisms survivand 5 other strains of bacillus and 3 strains of non- ing the effect of 0.25 units per ml. after 6 hr. of incubation were more resistant t o its action. This sporulating Gram-positive rod-shaped bacteria. These levabs had serological properties similar to resistance persisted through 4 subcultures and could S. GENGHOF, be increased 5-fold by serial transfers in broth conthose of S. SUZ~UUT~US.-DOROTHY EDWARD J. HEHRE, and JAMES M. NEILL. Proc. taining streptomycin. Washed organisms surviving after 5 hr. incubation with 7.5 units of streptomycin SOC.Exptl. Biol. Med., 61, 339(1946). per ml. were not more feSiStant.-DOROTHY HAMRE, (A. E. M.) DONOVICK.Proc. Penicillin-Difiusion of Sulfonamides and, into GEOFFREYRAKE,and RICHARD Fibrin. Using a m d i c a t i o n of the agar cup Soc. Exptl. Biol. Med., 62, 25(1946). (A. E. M.) method on agar and fibrin plates no evidence was found of penetration of sulfathiazole and sulfadiazine Sulfonamide Susceptibility of Stock Strains of into fibrin. Penicillin diffuses almost as well into Dysentery Bacilli and of Strains from Recent Epifibrin as into agar. I,t is suggested that the diffus- demics. The susceptibility of dysentery bacilli to ibility of penicillin into fibrin is a n important factor the bacteriostatic action of sodium sulfadiazine was in the &cacy of this substance in the treatment of determined by the use of a medium which was essubacute bacterial endocarditis.-M. H. NATHANSON sentially free of sulfonamide inhibitors. Of 219 and RUTHA. LIEBHOLD.Proc. SOC.Exptl. Biol. strains tested, 202 were susceptible t o the drug while (A. E. M.) Med., 62, 83( 1946). 17 strains were resistant. Among the susceptible Penicillii. Dried-Penicillin-Sensitive Oreanisms strains were representatives of each of the wellin. Dried iathogenic penicillin-sensitive osanisnis established varieties of Shigella. The resistant strains included representatives of Shigelkz @famay remain viable for a considerable period-at least 10 wk.-in contact with commercial dried peni- dysenteriue (Flexner types W. 2, and VZ) aiid Sh. sonnez. Many of the resistant strains were isolated cillin. This mixture when dissolved and injected into animals may cause infection. In practice the from patients who failed t o respond to treatment risk of infection from contaminated dried penicillin with sulfonamides. The results serve to emphasize is small, but it is sufficient t o make it advisable to the difficulty in the chemotherapy of dysentery.ALAN W. RERNHEIMER.Proc. SOG. Expll. B i d . test t h e sterility of dried penicillin before use.-H. (A. E. M.) Med., 61, 325(1946). PROOM. Lance;, 251, ll(1946). (W. H. H.) ~~

CHEMISTRY GENERAL A N D PHYSICAL Detergents-Solubhtion of Insoluble Organic Liquids by. Solubilization is attributed to incorporation of the insoluble substance within and upon the colloidal micelles of detergent. This study was a systematic investigation of the factors in organic

substances which determine the extent of solubilization. A number of cationic and anionic detergents were used with a series of aliphatic and aromatic hydrocarbons and a few polar compounds. The extent of solubilization decreases with an increased molecular weight and polar compounds are more solubilized than hydrocarbons. Although many

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PHARMACEUTICAL ABSTRACTS

generalities are possible, many specific conditions were encountered.-J. W. MCBAIN and P. H . RICHARDS. Ind. Eng. Chem., Znd. Ed., 38, 842 (M. W. G.) (1946). Measuring the Distribution of Particle Size in Dispersed Systems. A micromanometric method for measuring the size of dispersed particles is described. The apparatus is simple t o make and the measurements can be made rapidly with a reasonably high precision. The method may be applied t o both solids and concentrated emulsions.-W. M. DOTTS. Znd. Eng. Chem., Anal. Ed., 18,326(1946). (M. W. G.) Procaine Salts-Comparison of the Fixation of Charcoal as a Function of Concentration and Without Stirring of Various. The solutions were filtered through purified vegetable charcoal under identical conditions, and the adsorption of cation and anion was determined. Fixation increased in the order: isobutyrate, hydrochloride, phenylpropionate, monobasic citrate, dibasic citrate. This order is curious because the fixation is in the order of increasing surface tension, that is, in increasing order of those which accumulate less in the phase boundaries. In every case fixation of cation and anion was nearly equal, as though molecules of salt were adsorbed, although the compounds are known to be. highly BAZIN. and ionized.-TEAN RBCNIER. SUZANNE JACQUELINE FERB. Ann: pharm. franc., 3 , '61-64 (1945). (A. P.-C.) Soa s Effect of, on Mutual Solubility of Organic Liqui&.-The effect of soaps on improving the mutual solubility of glycols and hydrocarbon solvents was studied. The soap became highly soluble in the mixture even if it had a limited solubility in one solvent alone. Potassium and sodium stearate were more active than sodium oleate. Twelve per cent sodium oleate makes benzene and propylene crlvcol miscible in all DroDortions a t room temperaMCBAIN. %e.-sANTI R. PALIT-and JAMES Ind. Eng. Chem., Ind. Ed., 38, 74144(1946). (M. W. G.) Sodium Chloride-Eff ect of, on the Ionization Constant of Boric Acid and the pH Values of Borate Solutions. The PH values for solutions of borax (sodiuni tctraborate decahydratc) and sodium chloride were determined from 0" to GO" by the method of cells without liquid junction. I n onc series, the effect of sodium chloride on the apparent ionization constant of boric acid was determined by measurements of cells in which the concentration of borax was maintained constant (0.01 M ) while that of the sodium chloride was varied. I n a second series the pH values of various concentrations of borax in 0.01-M sodium chloride were measured, and in a third, similar measurements were made of solutions containing 0.023-M borax with a variable concentration of chloride. The values of other investigators for the pH of solutions of borax in which cells with liquid junctions werc involved are colnparcd with those currently report ed. Sonic of these arc modifictl t o take cognizance o f prcscnt-day views roiiccriiiiig electrolytic dissociation. A U.Ol-Alsolutioii o f bot-as (3.81 Gm. of borax per I,. of solution) is recommended for the calibration of pH equipment. Thc equation PH = 2331.7/T 0.017433T - 3.840, where T is the absolute temperature, represents the pH values for this solution from 0" t o 60".--Gao~G~ et al. J . Research Natl. Birr. Standards, G. MANOV, (W. T. S.) 36, 543-58( 1946).

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ORGANZC Alkaloids Cinchona Alkaloids-Ion Exchange Process for Extracting. Alkaloids of cinchona were extracted by

dilute acid and recovered by ion exchange in a cyclic system with an over-all yield of 81.2y0 within 82 hr. Either dried or undried bark may be used. Portable equipment may be used.-N. APPLEZWEIC and S. E . RONZONE.Ind. Eng. Chem., Ind. Ed., (M. W. G.1 38, 576( 1946). Garrya-The Alkaloids of Species of. I. Isolation of Alkaloids. Reports of the use of Garrya in treatment of intermittent fever prompted this investigation. Reference is made to the few mentions of Garrya in the literature. Experimental work is reported in detail. Six species were examined for alkaloidal content, G. jlavescens, G. fremontii, G. bwcifolia, G . elliptica, G. veatchiz, and G. wrightii. G. flauescens contained no alkaloid. All the others did, some being amorphous, others forming crystalline hydrochlorides. Two crystalline substances were isolated from the bark of G. veatchii and names suggested are garryine and veatchine.- J. F. ONBTO. J . A m . Pharm. Assoc., 35, 204(1946). (2.M. C.) Gelsemium Sempervirens-The Alkaloids of. Gelsemine and sempervirine were isolated in improved yields. Gelsemicine, probably G O H Z U O ~ N ~ , a secondary base, has been more fully characterized. Crystalline derivatives of further alkaloids have been obtained in small quantity. The catalytic hydrogenation of these three components has been studied. Gelsemine is a strong monoacid base ( K = 2.3 X lo+; the oxygen atoms are very inert and their function is still obscure. Moore's apogelsemine and isoapogelsemine ( J . Chem. Soc., 1910, 2223; 1911, 1231) appear to be produced by hydration of the o l e h i c linkage in gelsemine. Numerous exploratory observations on the degradation of gelsemine and sempervirine are recorded.-W. G. C. FORSYTH, 9. F. MARRIAN, and T. S. STEVENS. J . Chem. Soc., 1945, 579-82. (W. T. S.) Lobeliie-Determiqation of, in Lobelia and Tincture of Lobelii. The author has developed a specific method for the determination of lobeline in Lobelia and its tincture, which depends upon the fact that when lobeline is distilled with steam from a mixture having a pH between 6 and 10, one mol of acetophenone is split off quantitatively. The acetophenone can be determined in the distillate by adding an exccss of sodium hypoiodate to form iodoform, when after acidification the excess iodine can be back titrated with sodium thiosulfate: Results obtained with this method are more constant than those obtained by a n acidimetric titration, and furthermore the method may be used t o determine lobeline in mixtures containing other alkaloidal drugs such as belladonna leaf. I n determining lobeline .in lobelia, 10 Gm. of the drug is shaken in a 200-cc. flask for l / ~hr. with 100 Gm. of ether and 7 Gm. of ammonia water. The ethereal solution is Iiltered through a pledget of cotton, and 70 Gm. representing 7 Gm. of the drug is then filtered through filter paper into a separatory funnel. This ethereal solution is shaken with successive quantities of 10.5cc. and 5 cc. of 0.1 N HCl. The acidified aqueous solution is then filtered into a 100-cc. round-bottom flask, the filter being washed with a sniall quantity of water. Two drops of aqueous bromthymol blue (1 i n 500) is added followed by a saturated solution of sodium phosphate in sufficient quantity t o turn the liquid green. The contents of the round-bottom flask are then distilled with steam and the distillate condensed in an upright condenser. The distillate is caught in a n iodine-addition flask, under a small quantity of water, the distillatioh being continued until 50 cc. have passed over. Five cubic centimeters of MOJ, sodium hydroxide and 50 cc. of 0.01 N iodine are added t o the distillate, the flask stoppered, a n d the whole allowed t o stand for 30 min. ; 10 cc. of 38% HCI is then carefully added and the

CHEMISTRY flask again stoppered. After cooling the free iodine is titrated back with 0.01 N sodium thiosulfate.

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dilla seed under similar conditions. Use of white hellebore as a source of alkaloids could be considered only in case of acute shortage of sabadilla seed.P. MANCEAU, F. MONTANT, and G. N~TIEN. Ann. pharm. franc., 3, 11-14(1946). (A. P.-C.)

At the same time a blank is run containing 50 cc. of 0.01 N iodine. The difference in cc. of 0.01 N sodium thiosulfate times 0.562 is equivalent to the mg. of lobeline in 7 Gm. of the original drug. When the method is applied t o the tincture, 25 Gm. of the tincEssential Oils and Related Products ture is evaporated on a water bath until a small Absolute l of Lilly (Liium Candidum L.). aqueous residue remains. This is taken up in 20 Two samplesOiof different origins had the following cc. of 0.1 N HC1 ahd filtered; 2 cc. of ammonia analytical constants: specific gravity at 15" 0.9592, water is added and the mixture shaken out 3 times 0.9423; refractive index at 20" 1.4787, 1.4861; with 10 cc. of ether. The combined ether extracts acid 27.16, 19.6; ester value 122.04, 115.03; are shaken out with 5.2-cc. and 5-cc. portions of 0.1 ester valu'e after acetylation 220.24, and carbonyl N HC1. Two drops of aqueous bromthymol blue value value Codistillation with ethylene glycol (1 in 500) is added followed by a sufficient quan- under 18.9.22.4. 3 mm. pressure yielded 8.2% and 10.970, tity of a saturated sodium phosphate solution t o respectively, of colorless oils with the following turn the liquid green. The remainder of the assay constants: specific gravity at 15' 0.9013, 0.915; is conducted as described under 1obelia.-0. F. optical rotation at 20", 1" 28'. 0055'; refractive UPPELIB. I'hurm. Weekblad, 81, 41( 1946). index a t 20' 1.4681, 1.4764; acid value 12.62, (33.H. W.) ester value W.80. Thc following constituents Rauwolfia Vomitoria Afz-An African Aponycea. were identified ;p-cresol, linaloijl, a-terpineol, phenylHistologically the plant is similar t o the American ethyl alcohol esterified by acetic, cinnamic and species, Rauwolfia hctcrophyllu Roem. and Schult. palmitic acids. It is remarkable t h a t for a long time R. vomitoriu from French Guinea had the following perfumers have succeeded in reproducing the odor crude alkaloid content: root bark 1.1270, stem bark of the flower b y judicious mixtures in which fre0.55%; use of sodium hydroxide instead of am- quently predominate linalyl and terpinyl cinnamates monium hydroxide for the assay yielded 1.1770 and which are undoubtedly present in the flower.0.59%, respectively. The root bark was found t o (MRs.) M. G. IGOLEN. Parfumeric, 1, 132(1943). contain at least 5 alkaloids which had previously been (A. P.-C.) identified in other species of Rauwolfia, particularly The Aromatic Flora of Morrocco. Oil of Lavanserpentina Benth. (Ofihioxylon serpentinurn L.) : dula pedunculata Cavanille. The sample examined, ajmaline (0.037%): isoajmaline (0.074%), small originating in the Zaer region, obtained in 0.135 t o quantities of ajmalicine and ajmalinine, and traces O.25y0 yield by direct-fire distillation of flowers in of a yellow base (probably serpentinbe).-R. PARIS. May and June, had the following analytical conAnn. pharm. franc., 1, 13842(1943). stants: specific gravity a t 15" 0.9489, optical rota(A. P.-C.) tion at 20" -16", refractive index at 20" 1.4784, insoluble in 75% alcohol, soluble in 0.8 vol. of 85% White Hellebore (Yeratrum Album L.)-Extraction and Chemical Determination of the Total alcohol (with opalescence above 2 vol.), soluble in Alkaloids of, The alkaloid content is greatest when 0.1 vol. of 95% alcohol (with very slight opalescence) the plants are dried slowly in the shade; exposure to acid number 4.2, ester value 13.30, ester value after sunlight destroys an appreciable amount of the alka- acetylation 63.13, carbonyl value 107.52, cineole loids. The distribution of total alkaloids in the plant 5.5% (0-cresol), esters (as bornyl acetate) 4.90%, is approximately as follows: lower portion of the free alcohols (as borneol) 14.14%, total alcohols (as stem 10%. rhizome 15%, radicles 75%. The total borneol) 17.99%, l-camphor 29.18%, slight violet alkaloids content varies considerably from year t o blue with Beszonoff's reagent, brown coloration with year. The maximum yield of crude alkaloids ob- bromine in chloroform solution. The following comcarvacrol, 1-b-pinene, tained was 1%; the average yield for the best years pounds were identified: was 0.6% t o 0.7%. Acid extraction is long and tedi- cineole, free and combined I-borneol, 1-camphor, ous, does not remove the whole of the alkaloids, acetic acid (combined), I-cadinene. An unidentified yields a very impure product that is difficult t o purify compound (m. p. 108') was isolated. The conand is not suitable for commercial application be- stituents of this oil are essentially the same as those cause the extractors are usually of steel and are at- identified in oil of Lippia adoensis Hochst by Paltacked by dilute acid. Extraction in alkaline me- fray, Sabetay, and Petit [ Chimie b Industrie, 43, and G. ICOLEN. Pardium (preferably ammonium hydroxide) is rapid 367( 194O)].-J. GATTEFOSSE (A. P.-C.) and complete, requires less solvent (ether, chloro- fumerie, 1, 97-98( 1943). Essential Oil in Garlic Cloves-Determination of. form, trichloroethylene, 95% alcohol) which is almost completely recovered, gives light-colored solu- The following technique is recommended: grind 10 tions from which the alkaloids are precipitated in a Gm. of garlic cloves freed from their outer casing, satisfactory state of purity, and gives decidedly macerate 1 hr. in 300 cc. of water in a stoppered higher yields than extraction in acid medium. Of flask, add 20 cc. of alcohol and 2 cc. of oil, steam the various methods studied for the quantitative distill in a calcium chloride bath collecting in 10 cc. determination of total alkaloids: precipitation with of distilled water until 275 cc. has distilled, add 10 ammonia and weighing the precipitate gives more or cc. of decinormal silver nitrate, stoppered, let stand less impure alkaloids; the iodometric method (pre- in the dark for 24 hr., filter, wash 4 times with 20 cc. cipitation with Bouchardat's reagent, solution of the of distilled water, add 10 cc. of nitric acid and 10 precipitate in sodium thiosulfate. precipitation with drops of saturated ferric alum solution, and titrate ammonia, extraction with ether, and weighing) with decinormal ammonium thiocyanate (1 cc. = gives appreciably low results; precipitation as silico- 0.0057 Gm. of allyl sulfide). The oil consists of a tungstate requires the use of an empirical conversion mixture of complex sulfides which, during distillation factor but gives excellent results ; the volumetric are more or less dissociated by heat t o allyl sulfide, alkalimetric method gives excellent results with a and contains no allyl isothiocyanate. Under the little experience. I n commercial operations on 1000 above conditions, all the oil distills over in 275 cc.; Kg. of plant, using 5000-L., double-walled, hori- if more than 20 Gm. of sample is taken, results are zontal, rotary extractors, 3500-L. steam-heated stills, low due either t o incomplete hydrolysis of the gluco250 L. of 1 4 ammonium hydroxide and 3000 L. side or t o incomplete distillation of the essential oil. of trichloroethylene, yields of 6 to 7 Kg. per ton were Maceration with boiling water gives very low results obtained, as compared with 28 to 30 Kg. for saba- due t o destruction of t h e hydrolytic enzyme and

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6

PHARMACEUTICAL ABSTRACTS

also of the glucoside. Cold water maceration for 24 hr. is sufficient for complete hydrolysis of the glucoside. Crushing is necessary for complete recovery of the oil; cutting into pieces is insufficient. Use of Gros’ vacuum pipet [ J . #harm. chim., 19, 156,249(1934)] gives practically identical results, is quicker, but requires a special piece of apparatus. Fresh garlic cloves were found to contain 0.25% t o 0.29% essential oil (0.70% t o 0.75% on the dry basis); fresh stalks, 0.16yo(0.700/, on the dry basis). The Codex prescribes preparation of tincture of garlic b y maceration in 607, alcohol for 1Q days; a preparation with a higher oil content is obtained by maceration with water for 24 hr., followed by addition of 95% alcohol t o a total alcohol concentration of 60% and further maceration for 9 days. NOloss in oil content was noted after 6 mo. in tincture prepared by either the Codex or the modified Codex method; a 2% t o 20% loss was noted after 1 yr. Garlic cloves stored in a dry place progressively lose water, without appreciable loss of oil; the loss of water is greater if they are kept loose than if packaged in cellophane.-A. GUILLAUMEand H. BBGON. (A. P.-C.) Ann. pkurm. franc., 2, 9-14(1944). Essential Oils and Aromatic Compounds. Report of the annual meeting of the Essential Oil Importers’ Section of the London Chamber of Commerce and of the British Aromatic Compound Manufacturer’s Association held in May is given-F. G. PENTECOST. Perfumery Essent. Oil Record, 37, 155(1946). (A. C. DeD.) Natural Raw Material for the Perfumery Industry. Odorous principles can be divided into 4 main classes: natural, isolated, synthetic, and artificial. The origin, function, chief processes of preparation, main constituents, and most important raw materials of natural perfumes are briefly described aed discussed.-G. IGOLEN. Parfumerie, 1, 38-43( 1943). (A. P.-C.) Odor-Effect on, of the Existence of Rin s in Organic Molecules. The odorous character o? aliphatic compounds becomes remarkable only when they contain at least 6 carbon atoms and increases when there are 10 or more carbon atoms. I n view of the marked odorous character of aromatic compounds, it is suggested that the odor of chain compounds is related t o the flexibility of the chain which tends to bend into an unclosed ring, which tendency is influenced by the structure of the compounds (single or multiple double or triple bonds, saturation by hydration, etc.). Various examples are discussed in support of this hypotheSis.--GILBERT LANGLOIS. Pnrfumerie, 1, 239-40(1943). (A. P.-C.) Odor, and the Chemical Constitution of Organic Compounds-Relationship between. A general discussion reviewing: Devaux’s experiments on the emission of perfume from flower petals; the phenomena of cellular permeability in so far as they are involved in the mechanism of odor perception; variations in odor in relation t o the constitution of odorous molecules and as a function of the presence of certain radicals or of certain modifications of the molecules such as cyclization or of the relative positions of the “osmophores” they may contain; important’ constitutional analogies between odorous compounds, cyclic or acyclic, and relatively recently identified natural compounds such as “auxins” and “carotenoids.”-R. DELANGE.Parfumerie, 1, 12431( 1943). (A. P.-C.) Oil of Hybrid Lavender (“Lavandin”). The oil examined had the following constants and composition: specific gravity at 15” 0.8975, optical rotation 5’ 12’, total free CIOalcohols (cold formylation) 52.5%, CIOalcohols by acetylation in pyridine 7.8%. tertiary CIO alcohols (by difference) 44.7y0,, CIO ketones 12.1%, esters (as linalyl acetate) 24.5%. Fractionation of 2600 Gm. of oil in a 2-M. Dupont

column yielded 8 fractions which were examined with the following results. Fraction A, boiling point under 23 mm. 30’ t o 68” C., weight 89 Gm. consisting of: amyl ethyl ketone 1370, cineole about %yo,terpenes containing a-d-pinene about 607,, small quantities of an unidentified aldehyde, small quantities of an unidentified ester with amyl-like odor. Fraction B, distilled from 68” t o 95’ under 23 mm. pressure, weight 370 Gm. containing: tertiary alcohols (as linalool) (by difference) 22%, primary and secondary 1-octene-3-01s 3% t o so:, camphor 4%, 2-octene-3-01acetate 4y0, cineole l X o & . The undetermined 47% of this fraction most probably consists of terpenes containing at least 50yo of ocunene. Fraction C, distilled under 6 mm. pressure from 70’ t o No, weight 805 Gm. containing: linalool SS70, camphor 7%, small quantities of an unidentified primary or secondary alcohol ester. Fraction D , distilled under 6 mm. pressure from 80” to 87’, weight 507 Gm. containing: linalool about 75%, borneolS% to 9’%, camphor 8% to 9%. linalyl acetate 11%.small quantities of primary or secondary alcohols (possibly as acetates). Fraction E, distilled under 6 mm. pressure from 87” to 90”. weight 578 Gm. containing: linaloijl (P), a-terpineol or 1,Cterpinenol about 7%, d-borneol 12%, linalyl acetate %yo,linalyl formate 1% to 2%, probably also a very small quantity of terpenyl acetate. Fraction F, distilled under 6 mm. pressure from 90’ to 104’, weight 52 Gm., having specific gravity at 15” 0.9174, refractive index at 20’ 1.4632, optical rotation -7’ 44’. saponification value 205.5, CIO alcohols (acetylation in pyridine) 6%, CIOketones 3%. An accident prevented further study of this fraction. Fraction G, distilled under 6 rnm. pressure from 104’ to llOo, weight 70 Gm. containing: unidentified sesquiterpenes of the caryophyllene group, 1-octene-3-ol butyrate, geraniol together with another alcohol that is phthalizable in benzene solution (these alcohols are partly free and partly esterified as acetates, and possibly as butyrates), linalyl butyrate (the boiling point of the fraction does not justify the conclusion that it contains linalyl acetate), unidentified phenolic compounds. Fraction H , distilled under 6 mm. pressure from 110” to 140’ weight 31 Gm. containing: unidentified sesquiterpenes belonging mostly t o the caryophyllene group, small quantities of unidentified sesquiterpene alcohols and ketones, butyrates and another unidentified ester of a mixture of alcohols in which geraniol was identified. The approximate composition of the whole oil is: free tertiary alcohols 44% t o 45% (terpineol or 1,4-terpinenol 43% t o 44%); primary and secondary alcohols 8% (1-octene-3-01 about 0.7%. one or two primary or secondary alcohols O.l%, geraniol and its paragen about 0.2y0, d borenol 7%); aldehydes and ketones 12% (volatile aldehyde trace, amyl ethyl ketone about 0.4y0, aldehydes or ketones of which probably one is terpenic and one sesquiterpenic O.l%, camphor 11% to 11.5%); esters 24% t o %0/, (volatile ester with amyl-like odor trace, 1-octene-3-01 acetate 0.1%. acetate of one or possibly two primary or secondary alcohols 0.1%. terpenyl (?) acetate 0.1%. linalyl formate about O.2Yo, 1-octene-3-01butyrate, linalyl butyrate, butyrate and possibly acetate and another unidentified ester of geraniol and its paragen, linalyl acetate about 22%); terpenes 8% (ocimene 3 4%. d-pinene, other unidentified terpenes) ; sesquiterpenes 1% to 2% (sesquiterpene of the caryophyllene group); oxides 3% to 3.5% (cineole).-J. SPIRAS and L. VANDERSTREER.P a r f u w i e , 1, 235-38 (1943). (A. P.-C.) Oil of Lavender. The oil examined, obtained in 1.2y0 yield by direct steam distillation about Aug. 15 of Lavandula delphinensis plants grown at Moustiers-Ste-Marie at an altitude of 800 M., had the following analytical constants: specific gravity at

CHEMISTRY

7

Other Plant Principles 15" 0.8837, optical rotation at 20" -7' 46'. optical dispersion for I and V lines 1.70, optical dispcrsion Antibiotic Activity of Extract of Western Red for I and J lines 1.94, refractive index at 20" 1.4640, acid value 0.56, ester value 150.10, estei value after Cedar Heartwood. Water extract of western red cold formylation 218.84, ester 52.47%, free alcohols cedar heartwood inhibits the growth of a wide variety 21.35%, total alcohols 62.49y0, phthalization in of bacteria and fungi. The inhibition is due t o a pyridine 4.6% of alcohol (molecular weight 154). static effect only. The susceptibility is unrelated t o carbonyl value 11.74. The composition was studied the Gram-staining reaction and t o morphology. The on a 40-Kg. sample. The sodium bisulfite-soluble extract does not lose its potency by boiling or portion (80Gm. = 0.2%) was found t o contain (on changes of pH. It is not inactivated by urine and the basis of the original oil) : furfural trace, diacetyl gastric residue, but is inactivated by blood, serum, present, n-butyl aldehyde 0.0170, isovaleric aldehyde and cysteine. Large doses were nontoxic in the 0.0270, cyJ-hexenal 0.016%, n-octyl aldehyde o.0370, rabbit.-CHESTER M. SOUTHAM. PYOC. soc. Exptl. (A. E. M.) citronella1 0.016%, n-decyl aldehyde 0.0280J0, citral Biol. filed., 61, 391( 1946). Flos Spiraea-The Constituents of. The con0.016~0,cinnamic aldehyde 0.028%, unidentified aldehyde 0.02870. The sodium bisulfite-treated oil stituents of the flowers of Filipendula Ulmariu L. was extracted with cold (20") 3% sodium hydroxide official in Switzerland under the name of Flos t o remove phenols, lactones, and free acids, and the Spiraeae are not well known. The literature survey sodium hydroxide-soluble fraction was found t o have indicated lack of certainty in the identification of the following approximate composition (on the basis materials isolated and lack of agreement among the of the original oil): acetic acid 0.003%, n-butyric reported components. A steam distillation of airacid 0.002%. isovaleric acid 0.0007%, caproic acid dried drug of the 1942 crop before and after acid 0.0037%. capric acid 0.002570, unidentified acid hydrolysis indicated 0.04% free and 0.62% glyco(refractive index at 20' 1.5040) O.Ol%, unidentified side-bound methyl salicylate, identified b y odor and lactone O . O l ~ o , coumarin o.0470, unidentified phenol isolation of salicylic acid after saponification. There O.Ol%, thymol 0.005%, eugenol 0.005%. The resi- is apparently not more than 1%of this glycoside due from the sodium hydroxide extraction was present. Likewise there was found, identified, and borated by refluxing with n-butyl borate a t 150" quantitatively determined as the semioxamazone under 4 mm., the borates were saponified and the about 0.05% free and 0.26% combined salicylaldemixture steam-distilled, yielding about 20% t o 21% hyde. Free salicylic acid was not present in the drug. of free alcohols which contained (on the basis of the The 0.077, of salicylic acid found after heating the original oil) : low-boiling alcohols (including an un- drug 2 hr. with 5% sulfuric acid may have resulted identified alcohol with amyl-like odor) 0.1%. cthyl- less probably from a salicylic acid glycoside than amylcarbinol 0.0270, l-linalool 13%.-Lou1s B ~ N E - from a partial hydrolysis of the methyl salicylate. The small amounts of salicyl compounds in the drug ZET. Parfumerie, 1, 153-57( 1943). (A. P.-C.) Oils of Lavender-Presence of Normal Hexanol could hardly account for any beneficial effect of the in. n-Hexanol was found as esters (about 0.2%) drug. From the steam distillate of the unhydroin oil of lavender, and in the free state (0.5% t o lye) lyzed drug 0.006% of an acid of melting point 182' in oil of hybrid lavender ("lavandin").-L. B ~ N E Z E T(cor.) was isolated, and the same acid was found in amounts of 0.15% in extracts of the flowers. The and G. IGOLEN. Parfumerie, 1, 208(1943). colorless needles gave no reaction with ferric chlo(A. P.-C.) ride, gave a probable formula of CllH1204 and Synthetic Raw Materials for the Perfumery salicylic acid on vacuum sublimation, indiIndustry. Synthetic perfumes can be divided into yielded cating that the acid probably is a derivative of sali4 classes according t o the basic materials from which cylic acid. The amount obtained was too small for they are obtained, as follows: coal-tar derivatives, further work. The neutral substances, with a small castor oil derivatives, lialool and geraniol deriva- amount of volatile oil, formed a fat-like yellow mass tives, and sesquiterpene derivatives. An outline is having a refreshing terpene-like odor, which was not given of the more important perfumes of each class, further investigated. Treatment of the drug exwith an indication of the manner in which they are tracts with invertin, gaultherase, emulsin, and derived from the basic material.-MAx ROGER. rhamnodiastase gave no evidence for the presence Parfumerie, 1, 8-12(1943). (A. P.-C.) of water-soluble glycosides. A test for saponins with cholesterol gave a positive result. The following unknown or insufficiently identified materials were Fixed Oils, Fats, and Waxes found: A wax (1.5%) composed of a mixture of a Fatty Acids-Selective Absorption of. By subject- wax alcohol of the formula W S T O Hmelting 72ing the fatty acids of linseed oil and other vegetable 73.5' and its ester with stearic acid (acetate of the oils t o selective absorption on an aluminum oxide alcohol melted at 55-56'); a fat (about 0.5%) column it was found that the saturated acids accum- consisting of the glycerides of a-linolenic acid and of ulate in the upper part of the column. Magnesium stearic acid along with some oleic acid and lower oxide either alone or mixed with aluminum oxide or homologs of stearic acid; a saturated hydrocarbon phenol red was ineffectual.-A. SANTOS RUIZand M. (0.2% to 0.3%) of the formula C,,H312,+2.melting SANZMuRoz. Mon. furm.. 52, 83(1946). 63.544.5O (since the naturally occurring paraffins (A. E. M.) generally have unbranched chains this may correOils of Some Seeds of the Sudan. I n a survey of spond t o n-nonacosane for which a melting point of some oil-bearing seeds of the Sudan, the principal 63-64' is given); small amounts of a crystalline constants were given for the oils from Ocimum kili- steroid melting 260'; 0.0770 quercetin which appears mundscharuum, Euphorbia calycina, E . erytkraeae, t o be the same substance found by Loewig and Sterculia tomentosa and Trichilia enzetica. The oils Weidmann and called spiraeain; and a new querfrom the first three have strong drying properties, citin glycoside called spiraeoside. This new glycoand are good substitutes for linseed oil. The T . side was isolated in a total amount of 1.2% from emetica oil is excellent for soap-making. This oil various fractions of the acetone, ethanol, and methpossesses a bitter principle which is associated with anol extracts. It is apparently present in the flowers the nonsaponifiable portion. Each plant is discussed in higher concentration than the glycosides of methyl from the standpoints of its habitat, distribution, size salicylate and salicyl aldehyde. Spiraeoside crystalof its seeds, and the oil content of the seeds.-A. J. lized in yellow needles melting 209-211" (Pregl HENRYand D. N. GRINDLEY.J . SOC.Chent. Id., block). It was difficultly soluble in water as well as acetone and ether, more easily soluble in methanol, (W. T. S.) 63, 188-90( 1944).

8

PHARMACEUTICAL ABSTRACTS

ethanol, and wet ethyl acetate. It gave the yellow- against P. gallinaceurn ranged from ‘/N to =/Z.L. MAYand ERICHMOSETTIG.J. Org. green fluoroescence reaction of flavanols and was EVERJSTTE Chem., 11, 1-9(1946). (W. T. S.) reduced by magnesium in acid solution to a red py2 p Aminobenzenesulfonamidopyrimidiaesryllium compound. Hydrolysis with dilute sulfuric acid yielded one mol. quercitin and one mol. d- Preparation of, by a Novel Route. A series of sulglucose. It has the formula Cs1Hzo012.2HzO and a fanilamide derivatives of pyrimidine was prepared specific rotation (a)y = -69’ (methanol, 414.7 by allowing #-nitro-, #-amino-, or p-acetamidomg./lO cc.). The flowers are rich in tannin which benzenesulfonylguanidine t o react with 8-diketones explains their use as a styptic and astringent. The or 8-ketocarboxylic esters.-F. L. ROSE and G. authors found about 10.37” of tannin of the pyro-, SWAIN.J. Chem. Soc., 1945, 689-92. (W. T. S ) gall01 type. The treatment ,of the petroleum ether, acetone, ethanol, and methanol extracts are pre3-Azaphenthiazines-Synthesis of. l-Amino-3sented in chart form.-E. STEINEGCER and P. azaphenoxazine and 1,7-diamino-3-azaphenthiazinr CASPARIS.Pharm. Acta Helv., 20,154-73( 1945). were synthesized along with their intermediates, but (M. F. W. D.) these two compounds revealed no outstanding bacFluidextract of Hamamelis-Presence of Quer- teriostatic activity nor activity against T . equipercitol in. I n fluidextract of hamamelis prepared ac- durn infections in mice or PI.gallinaceurn in chicks.cording to the French Codex (lixiviation of the leaves V. A. PETROW and E. L. REWALD.J. Chm. Soc.. with 45% alcohol), there forms in time a brownish 1945, 591-93. (W. T. S.) deposit which was shown to consist essentially of Benzoic Acid from Phosgene and Benzene. By quercitol (3,5,7,3’,4’-pentahydroxyphenylbenzo-y-using aluminum chloride as a catalyst, benzene pyrone), the presence of which in hamamelis leaves reacts with liquid phosgene to form benzoic acid had not yet been recorded.-H. CANALand AND& more efficiently than using an inert solvent like carGORIS. Ann. phurm. jranG.. 2, 56(1944). bon disulfide. The yield depends on time and molar (A. P.-C.) ratios. The resultant benzoic acid is free of nuclear R. K. FRANTZ, +Sadonin-Constitution of. In addition to 1- chlorine.-W. H. C. RUEGGEBERG, santonin and 6-santonin a new compound, C I ~ I Z O O and ~ , A. GINSBURG.Ind. Eng. Chem., Ind. Ed.,38, (M. W. G.) was isolated from certain species of Artcrnesia. 624( 1946). Some physical and chemical properties of #+antonin DDT-Reactions of. The components of techniwere determined, but its structure was not estab- cal samples of the insecticide “DDT” have been lished.-G. R. CLEMOand WESLEYCOCKER. J. separated and identified, and their reactions have (W. T. S.) Chm. Soc., 1946, 30-36. been investigated. In addition to the main physiologically active product, 1:1:l-trichloro-2:2-di-(4Unclassijed chloropheny1)ethane(“pure DDT”), there are alAcridine Derivatives as Antimalarials. 2-Chloro- ways present the very feebly insecticidal isomer 5-(2/-diethylaminocyclohexylamino)-7-methoxyacri- 1:l:1 - trichloro 2 - (2 chlorophenyl) - 2 - (4dine, 2-chloro-5w-diethylamino-o-toluidino-7-meth-chloropheny1)ethane(“iso-DDT”) and small quantioxyacridine, 1-chloro-5-6-diethylamino-a-methylbu-ties of the physiologically inert “half condensation 1:1:1-trichloro-2-hydroxy-2-(4-chlorotylamino-9-methyladdine and l-chloro-5-8-diethyl- product,” amino--methylamino-8-methylacridine were pre- pheny1)ethane. When crude chloral has been used pared, and showed some activity against P. gallina for the manufacture of DDT there is also present ceum.-D. MURIEL HALLand E. E. TURNER.J. 1:l - dichloro - 2:2 - di (4 chloropheny1)ethane (“DDT”), which has only one-third of the insecti(W. T. S.) Chem. Soc., 1945, 694-99. cidal activity of “pure DDT.” Methods of analysis iso-Alloxazines, Quinoxalines,and Quinoxalocyclo- of technical DDT have been developed. The repentadienes as Antimalarials. Several iso-alloxa- duction of DDT affords an example of a reversed zines, quinoxalines, and quinoxalocyclopentadienes benzil-benzilic acid transformation, there being were prepared and found inactive against P. relicturn produced “DDD”, 1: ldi-(4-~hloso#henyl) ethane and P . gallinaceurn.-D. MURIELHALLand E. E. and 4 :4‘-dichlorostilbene. The nitration reactions TURNER.J. Chem. Soc., 1945, 699-702. of DDT, iso-DDT, and DDD have been studied. (W. T. S.) I n each case the nitro groups enter the positions 3 Amino Alcohols from 3-Methoxyphenanthrene as and 5 in the aromatic nuclei.-Jms FORREST, Antimalarials. A series of alcohols having the side OLIVER STEPHENSON, and WILLIAM A. WATERS. chain, CHOHCH~NRZ, in position 9 of 3-methoxy- J. Chem. SOL, 1946, 333-39. (W. T. S.) phenanthrene were prepared. The “quinine equiDialkylaminoalkyl Ethers of Aralkyl Alcohols. valents” of these alcohols against P. gallinaceurn Dialkylaminoalkyl ethers of aralkyl alcohols with ranged from l/1( to l/z. Thus the introduction of the the general formula Ar.XCY‘Y“02 (in which Ar 3-methoxy group failed to increase the effectiveness is an aryl radical, n is 1 or 2, X is a direct bond or as compared to the amino alcohols of phenanthrene. an organic radical which may also contain hetero The methoxy group had no effect in the toxicity of atoms, Y’ and Y” are hydrogen or hydrocarbon the compounds in chicks.-EmmTTE L. MAYand radicals, and Z is an N-disubstituted aminoalkyl ERICH MOSETTIG.J. Org. Ckem., 11, 15-20( 1946). radical) are prepared by 3 general methods: (1) (W. T. S.) a-substituted benzyl halides are treated with NAmino Alcohols from Phenanthrene as Anti- disubstituted amino alcohols in the presence of an malarials. A series of alcohols having the side chain, acceptor for hydrogen halides; (2) metal compounds CHOHCH2NRz,in position 9 of phenanthrene were of a-substituted benzyl alcohols are treated with prepared. The ‘‘quinine equivalents” of these alco- inorganic esters, e.g.. halides, of N-disubstituted hols against P. gallinaeum ranged from l/* to l/2, amino alcohols; (3) a-substituted aralkyl haloalkyl and thus were more effectivethan their analogs in the ethers are treated with secondary or tertiary amines. “tetrahydro series.”-EVERETTE L.MAYand ERICH The ethers thus prepared are therapeutic agents with MOSETTIG. J. Org. Chem., 11, 10-14(1946). an atropine-like antispasmodic action especially for (W. T. S.) the smooth muscular system of the intestines. They Amino Alcohols from Tetrahydrophenanthrene as also have a papaverine-like efficiency, they show Antimalarials. A series of alcohols having the side anesthetic properties, and they have bactericidal chain, CHOHCH~NRZ,in position 9 of 1,2,3,4- properties. Numerous examples are g’iven.-HENRT tetrahydrophenanthree were prepared. The approx- MARTIN,et al., assignors to J. R. GEIGYA.-G. U. S. (A. P.-C.) imate “quinine equivalents” of these alcohols pat. 2,397,799, April 2, 1948.

- -

=

-

- -

C H EM ISTKY P-Dialkylaminoethanols as Antimalarials. Aluminum isopropoxide reduction of the appropriate amino ketone produced the following compounds: (1) 01-( p bromophenyl)-j3-diethylaminoethanol,(2) -8- di- Npropylaminoethanol, (3) -&piperidylethanol, (4) -@di-N-butylaminoethanol. Salts of their amino alcohols were found t o possess antimalarial activity.NATHAN L. DRAKEand LEONGOLDMAN. J. Org. (W. T. S.) Chcm., 11, 100-4(1946). ~,~-Bis(34Dihydroxyphenyl) Alkanes-The Synthesis of Some. Synthesis of a,w-bis-(3,4-dihydroxyphenyl) alkanes was suggested because of the marked antiseptic and antioxidant properties of nordihydroguaiaretic acid. It was thought they might be useful antiseptics and antioxidants. Experimental work is given in detail. I n preliminary tests these compounds have antiseptic and antioxidant activities which compare very favorably with those of nordihydroguaiaretic acid .-OLE GISVOLD, DONALDBUELOW, and EDWARDH. CARLSON. J. Am. Phurm. Assoc.. 35, 188(1946). (Z. M. C.) Dimethyl Naphthols-Preparation of Some. $Santonin yields a dimethyl naphthol on fusion. As part of a program t o determine the structure of $santonin, the following: (1) 1,3-, (2) 3-4-dimethyl2-naphthol, and 2,3-dimethyl-l-naphthol were synthesized.-WEsLEY COCKER. J. Chem. soc., 1946, 36-39. (W. T. S.) Diphenylamine and 01, a-Diphenylmethylamine Derivatives as ChemotherapeuticAgents. The existence in mepacrine of the diphenylamine and a,adiphenylmethylamine ring-systems suggested the following amines NHR

R = CHa-CHz-NEtz

P

0

reinovc by recrystallizing from nitrobcnzenc, thc recommended solvent. This impurity can be removed in two ways: (1) by adding the product t o 0 times its weight of boiling Nalcoholic NaOH, filtering a t once, and then washing I with a small quantity of ethyl alcohol; (2) by dissolving the impure product (23 Gm.) in boiling aniline (350 cc.), filtering a t the boil, and filtering again at 25” at which temperature I is soluble t o 1%. The solubility of I in water is 0.05% a t 20°, but it may be rendered more soluble by the use of a hot diluted solution of lactic acid.- A. ALBERTand W. GLEDHILL. J. Soc. Chem. Ind., 63, 96( 1944). (W. T. S.) Patulin-Experiments Leading to the Synthesis of. Tetrahydrocomanic acid was prepared by catalytic hydrogenation of comanic acid and is identical with the acid CsHsO4. obtained by hydrolysis of patulin by HzS04. Ethyl tetrahydrocomanate, prepared by catalytic hydrogenation of ethyl comanate, was condensed with ethyl orthoformate to yield 3- or 6ethoxy-methy1enetetrahydrocomanate.-J. ATTENBURROW, et al. J. Chem. Soc., 1945, 571-77. (W. T. S.) Patdim-Experiments Relating to the Synthesis of. Ethyl acetopyruvate was condensed with HCHO in presence of aqueous KzCOS t o give 2,3diketo-4-acetyltetrahydrofuran, from which the corresponding enolic acetate, 2-keto-3-acetoxy-4acetyldihydrofuran, was prepared. The enolic ethyl ether, 2-keto-3-ethoxy-4-acetyldihydrofuran, was prepared from both compounds.-E. T. BORROWS and B. A. HEMS.J. Chem. SOC.. 1945,577-78. (W.T.S.) Penicillin-Pilot Plant Equipment for the Submerged Production of. Equipment for the submerged production of penicillin in 100-gal. quantities is described. Yields of 200-400 units per cc. could be obtained depending on t h e strain inoculated. Agitation and aeration were essential. A1 and Allegheny metal were nontoxic, but Fe is slightly toxic esDeciallv in a concentration above 500 Y. Der rr.~. -_. J.-J. ST~PANIAK, et al. Ind. Eng. Chem., Ind. Ed.. 38, 666-71( 1946). (M. W. G.) Piperidme Series-Experiments in. 3-Carbethoxy-1-methyl-4-piperidoneand the corresponding 3cyano compound were condensed with resorcinol t o give isomeric 3,4-3’. and 4’-tetrahydropyridocumarins : ~

M e N e c ) O H R = NH-CHpCH-CHnNEtz as antimalarials. These were synthesized a+ found \coo/ of no chemotherapeutic interest.-F. E. KING,T. J. I KING, and I. H. M. Mum. J. Chem. SOL, 1946, 5-10. (W. T. S.) OH 7-Methoxy-1-isoquinoline-The Synthesis of. A M e N 0 a synthesis of this compound from homophthalic acid in light steps is described.-HEmERT E. UNGNADE, \coo/ E. DOROTHYV. NIGHTINGALE, and HERBERT FRENCH.J . Org. Chem., 10, 533-36(1945). I1 (W. T.S.) which were converted into the gem-dimethylpyran 6’-Methoxyrubanol-9’-Synthesis of. Improvements have been made in the synthesis of this coni- derivatives : pound. Its optically inactive racemic ‘mixture M~N=( +) ( -) was shown to have between ‘/zand l / 4 the antimalarial activity of qUinine.-MORTON >co/ KLEIMANand SIDNEY WEINHOUSE. J. Org. Chem., Me? 10, 562-69(1945). (W. T. S.) I11 Nicotine-A Contribution to the Study of, and the Synthesis of 7-Azaindole and Derivatives.-G. R. OH CLEMOand G. A. SWAN. J. Chem. SOL,1945,603-7. M e N D - a (W. T. S.) 2 Nitro 5 amino 7 ethoxyacridine-Puri\co/ fication of. This compound (I), a n intermediate in Me/ the synthesk of “Rivanol,” is often contaminated with 2-nitro-7-ethoxyacridine,which is difficult t o IV ~

OH

+

~

-

- -

- -

10

PHARMACEUTICAL ABSTUCTS

The 7-alkyl derivatives of 111and IV were obtained by using orcinol or olivetol in place of resorcinol, but similar reactions of 4-n-hexylresorcinol were unsuccessful. The 7-amyl analog of IV was reduced t o the hexahydropyrido compound which was interesting as a possible analgesic because of its skeletal similarity t o hexahydrocannabinol and a spatial similarity to morphine.-R. M. ANEER and A. H. COOK. (W. T. S.) J . Chem. SOC.,1946, 58-60. Quinolyl Derivatives of p-Aminobenzamide. Three p-aminobenzamidoquinolines were prepared by reducing the corresponding nitro compounds obtained from p-nitrobenzoyl chloride and 5-, 8-aminoquinoline and 8-aniino-6-methoxyquinoline, respectively. These quinolines showed no activity against bird malaria nor against T . equiperduin and T . crziei infections in mice.-JOHN H. GORVIN. J. C k m . SOC., 1946, 61. . (W. T. S.) Refining Fat-Soluble, Vitamin-Bearing Materials. The undesirable tastes and odors of fat-soluble, vitamin-bearing materials can be substantially removed by heating to 160” to 180” with about 1% to 10% by weight of crude vegetable oil, preferably in an inert atmosphere and under reduced pressure. Example: Mix 50 parts of crude shark-liver oil with 2.5 parts of crude wheat-germ oil in the presence of nitrogen a t 1 mm. pressure and 170” for 5 min. t o obtain an odorless oil with the same vitamin A contcnt, without a fishy taste, and having about the same color as the untreated oil. Similar results are obtained by using crude corn-germ oil and crude soybean oil. Stability tests showed a marked decrease in.the amount of vitamin A destroyed after the addition of crude vegetable oils, which contain natural antioxidants.-LORAN 0. BUXTON,assignor OIL PRODUCTS Co. U. S. pat. 2,396,to NATIONAL 679, March 19, 1946. (A. P.-C.) Sterols-The Synthesis of Substances Related to dl-cis-Exdenin.-A. J. BIRCH,R. JAECER,and SIR ROBERTROBINSON.J. Chem. Soc., 1945, 582-86.

(W. T.S.)

ANALYTICAL Acetone-Determination of, by an Ultraviolet Spectrophotometric Method. A method is described for the determination of acetone in mixtures with diisopropyl ether, isopropyl alcohol, and lowmolecular weight olefins. The material is diluted with 2,2,4-triinethylpentane and the optical density P. V. measured a t 280 m p . 4 . L. BARTHAUER, JONES,and A. V. METLER. Ind. Eny. Chem., Anal. (M. W. G.) Ed., 18, 354( 1946). Aldehydes-A Study of the Determination of Some Official. Volumetric oxime methods and gravimetric methods using 2,4-dinitrophenylhydrazine as a reagent have been tried on benzaldehyde, cinnamaldehyde, and vanillin. Vanillin was used as the reference compound, its purity having been determined by a methoxy determination and melting point. Experimental work is given in detail and results are shown in several tabulations. Hydroxylamine methods of N. F. VII and N. F. VIII showed little difference, but the N. F. VIII was easier, especially for a n inexperieiiced operator. Getting corrcct end point requires careful matching. Wtth benzaldehyde, N. F. VII method gave low and inconsistent results; N, F. VIII gave higher and concordant results. Length of time of standing was unimportant with vanillin but of some significance in determining benzaldehyde and cinnamaldehyde. Addition of pyridine makes titration of a blank unnecessary but shows lower results. The 2,4-dinitrophenylhydrazine method was not satisfactory for vanillin and benzaldehyde. It was concluded that the N. F. VIII method is most suitable for benzaldehyde and cinnamaIdehyde.-MARY

ESTILLMARTIN, KENNETHL. KELLYand MELVIN

W. GREEN. J . Am. Pharrn. Assoc., 35, 220(1946). ( Z . M. C.) Aluminum-Determination of, in Alum-Precipi-

tated Biologicals. The following method of determining aluminum in biological materials, such as alum-precipitated diphtheria and tetanus toxoids is given: T o 10 ml. of a well shaken alum-precipitated toxoid, in a 250-ml. beaker, are added 5 ml. of coucentrated sulfuric acid and 1 ml. of concentrated nitric acid. The mixture is digested until cJpious fumes of sulfuric acid are produced. The clear colorless solution (which often contains aluminum sulfate crystals) is allowed t o cool to room temperature. One hundred fifty milliliters of distilled water is added and heated until the crystals of aluminuin sulfate dissolve. Add 10 ml. of a lOYo solution of NnlHPO,, followed by concentrated ammoilium hydroxide until a white precipitate forms. Concentrated hydrochloric acid is then added dropwise until the precipitate just dissolves. After heating to boiling for 3 to 4 min., add 5 ml. of 53% ammonium acetate and 3 ml. of glacial acetic acid. Allow t o cool to room temperature and filter the Alp04 precipitate on an ashless filter paper. Wash 3 times with hot distilled water t o get rid of the excess of sodium phosphate reagent. Finally, ignite the precipitate t o constant weight and weigh as AIPOI.-MARTIN BURGER. Chemist-Analyst, 34,89( 1945). (A. C. DeD.) Anions-Use of Selective Electrode for Determining, in Aqueous Solutions. If a chain is made up of an electrode of silver/silver chloride, the solution to be tested, and a calomel cell, the E. M. F. is a meaSure of the chloride content, in accordance with the Nernst equation. I n determining 43.5 t o 83.5 mg./L. of chloride, the results of 12 experiments all agreed within 1 mg. with values obtained by a titration method such as the Volhard procedure.D. MITOFFand E. SCHAAF. 2.anal. Chem., 127, 139-43( 1944). ( S . W. G.) Anthraquinone Compounds-Application of the Electrophotometer to the Determination of, in Rhubarb, Rhaponticum and “Polygonum” Preparations. Determination by means of the Meunicr electrophotometcr instead of Maurin’s colorimetric method [ B u l l . sci. pharmacol., 2 8 , 373-76(1921) ] is proposed. The technique is described in detail. The method is accurate t o within 10%. It is applicable only to drugs and preparations the chloroform extracts of which give reaction colors in alkaline medium which are approximately the same as that of pure emodin (Polygonum, Rheum), but is not applicable in the case of Cassia acutifoliu Del. C. occidentalis L., Andira araroba Ag.. Rhaninits ptirshiana D. C., R. cathurtica L., and Aloes species. Where applicable, the method has the advantages of rapidity (1hr. and 30 min.) and of requiring only small samples.-M. M. JANOT and A. MOREL. A n n . pharm. f r a q . , 2 , 7-9(1944). (A. P.-C.) Aromatic Hydrocarbons-Determination of Small Amounts of, in Aqueous Solution. By the use of a formaldehyde-sulfuric acid reagent, aroniat ic hydrocarbons in aqueous solution may be deterniinrtl with an accuracy of 10% in amounts from 1 to 500 p. p. m. The sensitivity is 0.0001 Gm. of aromatic hydrocarbon.-1-1. E. MORRIS,R. B. STILES, and W. H. LANE. Ind. Eng. Chem., Anal. Ed., 18, 294( 1946). (M. W. G.) Arsenic, Radioactive, of 90-Day Half-LifeAnalytical Procedure for Measurement of. T o determine radioactive arsenic of 90-day half-life, the arsenic is reduced t o the metal by hypophosphite. The metal is collected on a Selas filter plate and the radioactivity is then measured inside the chamber C. HENRIQUES, of a Lauritzen electroscope.-F.

CHEMISTRY

11

JR., and CHARLESMARGNETTI.Ind. Eng. Cheni., used for the detection of certain esters of p-hydroxybenzoic acid. The reagent is a freshly prepared Anal. Ed., 18, 415-17(1940). (M. W. G.) 2-Arylmethylimidazolies-Photometric Deter- solution of 0.1 Gm. m-nitrobenzaldehyde in 10cc. mination of. I n a prior paper [Farm. Revy., 45, concentrated suKuric acid. After determining the 213( 1946) ] was summarized the principles governing presence of the phenyl or cyclohexenyl radical, the the condensation of aromatic nitro compounds with test with m-nitrobenzaldehyde can be applied. T o compounds containing active methylene groups t o a small sample of t h e substance in a test tube is yield colored solutions for photometric analyses. added 2 drops of the reagent (or more depending The nitration method is now applied to the estima- on the amouut of unknown used). Phanodorn or tion of 2-benzylimidazoline (Priscol) and 2 4 1- evipan when heated carefully over a small flame naphthyl) ‘ methylimidazoline (Privine) . Method developed a red color which resembles the tint of a fresh solution of cochineal with quantities greater for Priscol: A specimen corresponding t o 25-150 than 0.03 mg. and a rose color with smaller quany of benzylimidazoline HC1 is exhaustively extracted with ether from alkaline solution. The ether is tities. The limit of sensitivity is 0.005 mg. The evaporated in a small dish. The residue is treated following medicaments give no reaction : anesthesine, novocaine, stovaine, tropacaine. cocainc, with 0.3 ml. of fuming nitric acid on the water bath and the excess acid evaporated just t o dryness. veronal, luminal, prominal. urethane, phenacetin, On cooling, the residue is dissolved in C. P. acetone dimethylaminoantipyrine and atoxyl; -while the following gave a more or less prominent yellow containing 1% absolute alcohol. The volume of solution is adjusted t o 10 ml., there is now added 5 coloration : orthoform, acetanilid, dial, antipyrine, drops of 3% solution of K methoxide in methyl sulfanilaniide, and nicotinamide. A yellow color alcohol to develop the color and t h e extinction is in the cold turning brown on heating was obtained read promptly (in 1 min.) in a photometer at about with methyl salicylate, salol and resorcinol; or 530 q.~ (the color fades rapidly). Methodfor Privine: orange with cryogenin. A red color was obtained Extraction and nitration is conducted as above. with sedormid, phanodorn, and evipan or red brown DESHUSSES.Pharm. A d a The residue is dissolved i n C. P. acetone containing with proponal.-J. (M. F. W. D.) 5% absolute alcohol and the color developed with Helv., 20, 199-200(1945). K methoxide. After volume adjustment t o 10 ml., Bromoform-Colorimetric Determination of, in the extinction is read at about 500 mp. The color is Compound Medicines. The following method for stable for over 3 min. Extinction curves of the the microdetermination of bromoform is based on color complexes of both drugs are depicted. Ap- Crump’s reaction. Take 10 cc. of an appropriate plication of the method t o determine privine in a dilution of the bromoform and dilute with water to jelly remedy known as Rhinogallae Rimidol (the 50 cc. (the solution should contain 1 to 4 mg. of formula is cited) is described. Here the prelim- bromoform per cc., preferably 2 t o 3 mg.) ; to 1 cc. inary extraction is as follows: 0.500 Gm. of the of the solution in a d r y test tube add 2 cc. of exjelly is suspended in 10 ml. of water in a separatory temporaneously prepared 20% &naphthol solution funnel and acidified with 2 ml. of 2 molar HC1. in 95% alcohol and 2 cc. of sodium hydroxide soluThis is now extracted 3 times with 10-ml. portions tion (concentration not speciiied, but presumably of ether and the ether discarded. The aq. phase is 5oy0);prepare a second identical tube; immerse both now made alkaline with 5 ml. of 2 molar NaOH and tubes in a waterbath at 80O, shake at the end of 30sec. extracted 5 times with 10-ml. portions of ether. and of 60 sec., remove one tube from the water bath After filtration of the combined ether solutions the aftergoand theotherafter 105sec.. allow tocool(the volume is adjusted t o 50 ml. and 5 ml. of the solu- blue color changes t o green and yellow, but this is tion is aliquoted and evaporated in a small dish on of no account); transfer the contents of each tube the water bath for nitration and determined as t o a 25-cc. volumetric flask, washing the tube and above.-T. CANBACK.Farm. Revy, 45, 377(1946). making t o volume with 10% sulfuric acid b y volume (C.s. L.) in 50% alcohol by volume; examine spectrophotoAscorbic Acid-Observations on the Titration of. metrically. The use of 2 tubes is advisable to enChecks on the stability of solutions of ascorbic acid sure t h a t heating has been properly carried out, indicate an initial rapid fall in ascorbic acid content but is not indispensable. Amounts under 4 mg. of followed by a leveling off to a fairly constant con- bromoform in 1 cc. can be detected with a n apcentration for periods as long as 6 wk. I n all cases, proximation of 1% under the most favorable condithe break in the deterioration of the ascorbic acid tions; the total relative error of the technique came when the growth of microorganisms became should not exceed 2% to 3% if instructions are macroscopically visible. The organisms were strictly followed. The reaction i s highly specific mostly molds whose growth was somewhat restricted and is unaffected by inorganic halides or even orby the lack of optimum medium. The oxidation of ganic halides having a structure closely related t o the ascorbic acid was greatly slowed down or pre- t h a t of bromoform (e.g., hexachloroethane, trichlovented entirely. Several ideas are suggested as an roacetic acid). The only interfering substances are explanation of this phenomenon. In another set of those having the general formula CHXs (particularly studies the influence of ferrous sulfate on the cata- chloroform) and those which can yield such comlytic oxidation of ascorbic acid was investigated, pounds under t h e action of alkalies (e.g.. chloral). using a molar ratio of ascorbic acid t o ferrous sulfate The various steps of the technique were investiof 1OO:l and 1:1, and titrating the solution after gated, and the above procedure was found t o give varying periods of time with dichlorophenolindo- optimum results. Application of the method to phenol. It was found that when the titration was the assay of specialties (in the form of sugar-coated carried out in the presence of acetic acid, the ferrous tablets) showed frequent deficiencies, ranging u p t o sulfate did not interfere, but if metaphosphoric acid 100% of the labelled content. This is attributed was used t o acidify the solution, the ferrous sulfate chiefly t o the volatility of bromoform. Even when the latter is combined with hexamethylenetetramine, reduced the indicator, giving erroneous results.-L. considerable loss of bromoform can occur during SIEFERT.Phurm. Acte Hek., 20,270-73( 1945). tabletting, unless special precautions are taken at all (M. F.W. D.) of manufacture.-RoBEkT PAULAIS.Ann. Barbiturates Containing the Cyclohexenyl Radi- stages (A. P.-C.) cal-New Reaction of. A reaction proposed by @harm. franc. 2, 99-102(1944). Reif and Barries [ Bbchem. Z.,277,328(1935)] was Casein-A Color Reaction of. Casein and ethyladapted t o the detection of barbiturates con- ene chloride, in the presence of Concentrated hytaining the cyclohexenyl radical. I t may also be drochloric acid, give a reddish purple color. It

12

PHARMACEUTICAL ABSTRACTS

forms slowly on standing at room temperature but quickly on moderate heating. Similar but much lighter colors are obtained on heating, when the ethylene chloride is replaced by trichloroethylene, carbon tetrachloride, or even benzene. The color does not develop when nitric or sulfuric acid is substituted for the hydrochloric acid. As other proteins have not been tested, it is not kuown whether this reaction is specific for casein: -E. WM. ROTH. Chemist-Analyst, 34, 87(1945). (A. C. DeD.) Cations-A Semimicro Scheme of Qualitative Analysis for the, Without the Use of Hydrogen Sulfide. A new approach to the development of a nonhydrogen sulfide scheme of qualitative analysis for cations has been achieved by not only controlling precipitation by ditferences in solubility products but by combining this principle with control of concentration of cations through instability coiistan ts of complex compounds.--J. T. D O n B I N S and E. S . GILRBATII.J. Chem. Rducnlion, 22, 119 (1945). (E. L. C.) Chlorinated Xylenol Mixtures-The Analysis of, with Especial Reference to the Unchlorinated Phenols Content. Chlorinated xylenol mixtures (including neighboring homologs) have been introduced as a substitute for scarce p-chloro-m-xylenol in the field of preservatives and disinfectants. The unchlorinated phenols in such mixtures can bc estimated by efficiently fractionating the mixture i n uacuo, whcreby the unchlorinated phenols, together with some monochlorinated phenols, are separated from other mono- and poly-chlorinated phenols. A chlorine determination of the former fractioii makes it possible to calculate the per cent of “free” phenols in the original mixture. Details of the method are given. It is likely that this method can be used with chlorocresol mixtures.W. H. RITCHIEand W. E. HAMER. J. Sac. Chem. Ind., 63, 247-49( 1944). (W. T. S.) Chromatographic Analysis-High-speed Filter Aid for. Celite number 545 may be used in place of super-cell as a n adsorbing agent in chromatographic analysis and has the advantage of speed.J. B. WILKES. Ind. Eng. Chern., Anal. Ed., 18, 329( 1946). (M. W.G.) Cider-Detection of, in Grape Wine. I n contrast to grape wine, cider contains as the characteristic component the alcohol sorbitol, and adulterations of grape wine with cider may, therefore, be detected by the presence ,of sorbitol. I n 1928 benzaldehyde was suggested as a reagent for the detection of sorbitol and the method was improved in 1931 by Litterscheid using o-chlorobenzaldehyde in place of benzaldehyde. I n the presence of acid, sorbitol and o-chlorobenzsldehyde condense to give almost quantitatively tri-(a-chlorobenza1)-sorbitol. The solubility of the condensation product limits the sensitivity of the test t o the detection of not less than 2.5% cider in the wine. The test is carried out as follows: 100 cc. of the wine is decolorized with 5 Gm. animal charcoal and concentrated t o 5 cc.; the tartar is removed by filtration or centrifugation, after which 10 cc. fuming hydrochloric acid and 8 drops o-chlorobenzaldehyde are added, the mixture shaken often and filtered after 24 hr. through a weighed porous glass filter, the residue washed 3 times with methyl alcohol, dried. and weighed. From the weight of the residue the amount oflsorbitol in 100 cc. wine may be calculated.-DR. E Y . Schweiz. Apoth.-Ztg., 83, 605-7 (1945). (M. F. W. D.) Citrate Ion-Determination of the, in *Aminobenzoyldiethylaminoethanol Citrate. p-Aminobenzoyldiethylaminoethanol (procaine) base is precipitated as silicotungstate, the citrate is oxidized t o acetone with potassium permanganate via Taiifel und Mayr [ 2.anal. Chem.,Pd,1(1983) 1, the acetone

is distilled into an alkaline solution and determined iodometrically. Dissolve a sample containing 0.03 to 0.06 Gm. of citric acid in 20 t o 50 cc. of distilled water, add 10 cc. of normal hydrochloric acid followed by a 5% silicotungstic acid solution (0.17 cc. per mg. of procaine), make t o 100 cc., shake, filter; neutralize a 50-cc. aliquot to phenolphthalein, bring t o p H 2 by addition of 3 cc. of buffer solution (100% phosphoric acid 49.03 Gm., crystalline monopotassium phosphate 68.08 Gm., water t o 1 L.),distil into 15 cc. of N/5 potassium hydroxide cooled in ice while adding to the boiling solution a 0.05y0 permauganate solution a t the rate of 1 drop per sec. until the red color persists 5 min., continue boiling for 20 miii., to the distillate add a measured quantity (e.g., 20 cc.) in excess of decinormal iodine, let stand 20 min., acidify with 8 t o 10 cc. of 25y0 sulfuric acid, and titrate with decinormal thiosulfate in presence of starch; 1 cc. of decinormal iodine = 0.00350 Gni. of citric acid. If the distillation is carried out propcrly the error does not exceed 1%. The method is suitable for quantities of 0.01 to 0.10 Gm. of citric aCid.-sUZANNE BAZIN. Ann. phurm. franC. 2, 14-16( 1944). (A. P.-C.) Colorimetric Determination of Calcium. A method for determining calcium colorimetrically as ’ residual permanganate with any one of a number of modern photolectric colorimeters or spectrophotometers is described. The method is applicable to the analysis of waters, brines, chemical reagents, biological materials, and foods. It is particularly convenient and time-saving when a number of samples are t o be analyzed simultaneously.ROBERTE. SCOTT and C. R. JOHNSON. ChemistAnalyst, 34, 81(1946). (A. C. DeD.) Conductometric Titrations with OrganicReagents. Determination of Copper with Cupferron and Iron with Sulfosalicylic Acid. I n sulfuric acid solution, cupferron is suitable for determining copper by conductometric means. This may be applied t o brass without the removal of tin and lead. Similarly sulfosalicylic acid and its ammonium salt may F. CORWIN be applied t o iron determinations.-J. and H. V. MOYER.Ind. Eng. Chem.. Anal. Ed., 18, 302( 1946). (M. W. G.) Copper-Separation of Cadmium from, with Sodium Thiosulfate. Vortmann (2.anal. Chem., 20, 416(1881)) recommended the use of sodium thiosulfate for precipitating cuprous sulfide in the presence of cadmium ions; the latter remains in solution as complex thiosulfate. If much coppex or cadmium is present, however, a single precipitation is inadequate, as the cuprous sulfide invariably contains some cadmium sulfide. The first cuprous sulfide precipitate, therefore, should be ignited to form cupric oxide and fused with potassium pyrosulfate. Extraction with water gives a solution from which a second treatment with sulfuric acid (12 cc. of 18 N acid per 100 cc. of solution) and an excess of sodium thiosulfate solution gives copper sulfide. As much as 0.15 Gm. copper as cuprous sulfide can be easily converted t o cupric oxide by roasting in the air and this is recommended for the gravimetric determination. In the filtrates from t h e cuprous sulfide precipitations the cadmium can be precipitated as cadmium sulfide after removal of most of the sulfuric acid and the sulfur that precipitates. The cadmium can be precipitated as cadmium sulfide from a solution which is not over 1 N in acid and contains not more than 0.2 Gm. cadmium. The cadmium sulfide can be weighed as such or converted into cadmium ammonium phosSARUDI.2. anal. Chem.. phate monohydrate.-I. 127, 161-67( 1944). (S. W. G.) Copper-Simple Method for the Microdetermination of, by Delepine’s Reaction. The method is based on the color produced by copper with di-

CHEMISTRY

13

2,4-Dinitrophenylhydrazones-Separation of, by ethylthiosulfocarbamic acid in aqueous acetone solgtion. Measure 10 cc. of the solution (urine, Chromatographic Adsorption. Several 2,4-dinitroblood serum) into a 150-cc. Pyrex Kjeldahl flask, phenylhydrazones were studied for adsorption on add 1 cc. of 1% disodium hydrogen phosphate and silicic acid mixed with Super Cel and found to be 10 cc. of nitric-perchloric acid (100 cc. of nitric acid adsorbed in the following order: acetaldehyde, aceof specilic gravity 1.39 and 40 cc. of perchloric acid tone, propionaldehyde, and methyl ethyl ketone. of specific gravity 1.61), add 2 small glass beads Each could be separated from mixtures of the others (diameter 3 mm.), place the mouth of the flask in the except acetone which could not be separated from opening of a Guillaumin suction apparatus, heat propionaldehyde.-J. D. ROBERTSand C. GREEN. very gently to boiling, boil gently until the protein Ind. Eng. Chem., Anal. Ed., 18,335(1946). (M. W. G.) coagulum is completely liquefied, boil more rapidly until nitrous fumes begin to come off, lower the Disodium Hydroxymercuridibromofluoresceinheat and continue boiling to evolution of white Use of, as Alkalimetric Indicator. Attention is perchloric acid fumes, gradually increase the heat, drawn to the suitability of Mercurochrome as indievaporate to dryness and finally to fusion and sub- cator, preferably for titration of alkaline solutions. limation of the ammonium perchlorate. Let cool, Its fluorescence in alkaline solution practically disadd 2 cc. of quarter-normal hydrochloric acid, appears at pH 4.6 to 4.5, the end point being interdissolve the residue by progressively heating t o mediate between that of methyl orange (PH 4) and boiling with a swirling motion of the flask, let cool, methyl red (pH 5). At the end point there forms a add successively drop by drop with continuous red precipitate which colors the solution a light agitation 8 drops of ammonium hydroxide, 0.5 cc. pink. It is suitable for the titration of strong of 1% alcoholic solution of diethylthiosulfocarbamic acids, strong bases, and weak bases having a disacid [prepared v i a MacFarlane, Biochem. J.. 26, sociation constant of 10-7.6 or more (ammonia, 1022(1932)], and 3 cc. of pure acetone (the brown methylamines, numerous alkaloids, one hydrogen copper complex which precipitates redissolves, of phosphoric acid, sodium carbonate, sodium and various mineral compounds precipitate out), bicarbonate, borax in the absence of glycerol, etc.) .transfer to a 10cc. graduate rinsing the flask with LOUISDOMANGE.Ann. pharm. frang.. 2, 5556 acetone and making to 10 cc. with acetone, mix by (1944). (A. P.-C.) vigorous shaking, let stand 5 min.. fdter on filter Electronic Make and Break Operation. Depaper washed with hydrochloric acid; after at scription of an apparatus.-R. B. HARVEY.Ind. least 10 rnin. and at most 1hr. make the colorimetric Eng. Chem., Anal. Ed., 18,331(1946). measurement with a Meunier electrophotometer or a (M. W. G.) Duboscq colorimeter. Run a blank on the reagents Erythrol Tetranitrate-Saponification Equation and correct if necessary. Justification is given for the various steps of the technique.-PAvL FLEURYand Determination of. In the saponification of erythrol tetranitrate, instead of the theoretical 4 and JEAN COURTOIS.Ann. phurm. frang., 3, 14-22 hydroxyl groups, values are found ranging in the (1945). (A. P.-C.) Copper-Use of an Ion-Exchange Resin in De- neighborhood of 6.5, according to experimental termination of Traces of. Copper in traces in conditions. Considerable quantities of formic acid powdered milk and ice cream mixes may be deter- are formed during saponitication, and also of nitrites mined rapidly by omitting acid digestion or ignition which may be measured colorimetrically by the and using the method described herein. The pH Griess reaction to determine erythrol tetranitrate, of the sample is reduced with perchloric acid and the in the same manner as used by the author to dctcrcopper is adsorbed in an ion exchanger and later mine glycerol trinitrate [Gallia Phurm Acta, 1, stripped with hydrochloric acid and determined 159-67( 1943) 1. In very dilute solutions, after po1arographically.-H. A. CRANSTON.Ind. Eng. saponification with a large excess of potassium hydroxide, the ratio of nitrite nitrogen to total nitrogcn (M. W: G.) Chem., Anal. Ed., 18,323(1946). Cresyl Phosphate-Detection and Determmation is approximately 0.61 as compared with 0 66 for of, in Vegetable Oils. Cresyl phosphate is added to glycerol trinitrate. For deterniination in mixture\, reduce g u n + n g and resinification of lubricating erythrol tetranitrate is first separated by steam disvegetable olls that were formerly used only for food tillation. If both erythrol tetranitrate and glycerol purposes. The use of such technical grade oils trinitrate are present together, the product is exfor food purposes may produce intoxications, more tracted with alcohol to obtain a concentration of particularly polyneuritis. Method: Reflux 10 Gm. about 1% in erythrol tetranitrate or glycerol triniof oil and 60 cc. of twice normal alcoholic potassium trate, and the extract is diluted with 10 vol. of hydroxide for 1hr., cool, add 60 cc. of water, evapo- water; glycerol trinitrate slowly precipitates out in rate on the water bath t o remove the alcohol, add crystalline plates, and 90 to 95y0 of it can be sepa60 cc. of water and 30 Gm. of sodium chloride, rated by filtering after standing several hours. shake with warming to dissolve the sodium chloride, Erythrol tetranitrate and glycerol trinitrate can cool, make t o 200 cc., and filter t o remove the salted- then be determined separately (with an approximaout soaps. Phosphates and cresol can be deter- tion Of 10 to 15%).-ROBERT PAWLAIS An??+. (A 1’-C) mined in the clear filtrate by known methods. phurm. franc., 3, 73-75(1945). Estrone in Oil Solutions of Estrogens - The DeAgreement between the cresol and phosphate contents is coniirmatory evidence of the presence of termination of. Since pharmaceutical preparations cresyl phosphate. Use of sodium phosphate for containing natural estrogens dissolved in vegetable “regeneration” of the oil can destroy completely the oils are widely used, it is very desirable t o have an value of the phosphate determination, and in such a accurate and reasonably rapid method for, the decase only the detection of a phenol compound termination of estrone in them. Many methods volatile with steam is of any value.-P. MALANGEAU.are found in the literature and brief reference is made to some of them. The method reported is Ann. phurm. franG., 2, 102-3(1944). (A. P.-C). DDT-Field Test for Surface. To determine based on the extraction of phenolic steroids by means DDT on surfaces in the field, the object is wiped of immiscible solvents, separation of estrone and with a swab containing mineral oil. This is then other phenolic ketosteroids by an adaptation of subjected t o a modified xanthydrol-potassium Girard’s reaction, determination of separated mahydroxide-pyridme reaction which gives a red color terial by ultraviolet spectrophotometry. Details with DDT.-H. A. SRFF. JR., and J. C. CASTILLO. of experimental work are given: apparatus, reagents, standard solution, and method. This Ind. Eng. C h m . , Anal. Ed., 18,316(1946). gravimetric method is applicable when the sample (M. W. G.)

PHARMACS~CAL ABSTRACTS

14

__

u contains 5 mg. or more of the phenolic ketosteroids. N -0 Samples containing less than 5 mg. may be analyzed by application of the spectrophotometric method R.CO(NHOH) 4-F e + + + = R-C (2) (0 Fe/3 to the residues obtained by the gravimetric proceA. ROTONDARO. dure.-JONAS CAROLand FELICE J. Am. Phurm. Assoc., 35, 176(1946). -U. T. HILL. Ind. Eng. Chem., Anal. Ed., 18, 317(1946). (M. W.G.) (2.M. C . ) Ether-Detection of Acetone in, by the Codex Filter Rods in Qualitative Analysis. Sintered Test. The Codex test (intermittent shakingover a glass filters have not been very successful, but if a period of 1 hr. of 20 cc. of ether yrith 2 cc. of mercuric filter rod is attached t o a glass tube with 2 rightsulfate solution in the cold) does not detect acetone, angle bends and during the filtering the tube is not auy precipitate formed being due t o vinyl alcohol in contact with precipitate the filtrate can be reor ethylene derivatives. If the mixture is placed in moved very satisfactorily from the precipitate. a water bath and the temperature raised progres- Similarly in gravimetric analysis, filter tubes used sively to the boiling point and held there for a in this way are convenient when a double precipitamaximum of 10 min., if ethylene derivatives are ab- tion is required.-JENO PLANK.z. anal. Chem., ( S . W. G.) sent acetone will give a white precipitate. The 127, lSCrSl(1944). test, is sensitive t o 1 :50,000. RothCa's reaction. of, in Water by Fluoride Ion-Determination however, is considered preferable because it is Means of a Photoelectric Colorimeter. This more specific. To 10 cc. of ether add 4 or 5 drops of method is based on the bleaching of a lake formed 5% sodium nitroprusside, 2 t o 3 Gm. of ammonium from a zirconyl salt and sodium alizarin sulfonate acetate, and about 1 cc. of ammonium hydroxide. by the action of fluoride ion. The photoelectric Presence of acetone is indicated by a violet red colora- colorimeter used is of the direct reading type based tion. The test is sensitive to 0.005% acetone in on that developed by Evelyn but differs from it in ether.-H. CARONand D. RAQUET.Ann. +harm. that the light passes vertically through a long abfranG., 2, 128-29(1944). (A. P.-C.) sorption cell rather than horizontally through an Extractum Filicis-Estimation of, by Chemical absorptioti cell consisting of a large test tube. By and Biological Means. A modified method of calibrating the galvanorncter scale against solutions determining crude filicin in Extractum Filicis is containing known amounts of fluoride, the p. p. ni. described (error less than 3%). After stirring the of fluorides in water can be determined. The data extract for some minutes, 3 Gm. is weighed out and thus obtained agree with those from the corresponddissolved in 40 ml. of cther. The solution is trans- ing visual method.---&%MAN JAMES WALKERand CLEMENTS GAINER. Can. J. Research. 23B, ferred to a separatory funnel containing 10 ml. of 370 GORDON (W.T.S.) BaOH solution. The mixture is shaken 3 min. 275-80 (1945). After standing 60 min. and obtaining a clear layer, Galenical Opium Preparations-Analysis of. there is tapped off 85 ml. of the aqueous phase. The method of Mannich for the determination of This solution is acidified with 20 ml. of diluted morphine (I) in opium used to advantage for the HCl. The precipitated crude filicin is then shaken assay of Pulvis ipecacuanhae opiatus, (11) Tinctura out with ether (25-,15-, and 10-1111. portions). opii crocata, and Tinctura opii benzoica. The The ether solutions are combined in a tared vessel following procedure is given for (11) : Triturate 5 and ether removed on a water bath. The flask is Gm. of I1 with 0.5 Gm. calcium hydroxide and 5 cc. dried a t 80' in an oven. The weighed residue water and after the addition of 20 cc. water allow to corresponds to 75y0of the total crude filicin content. stand for ' / t hr. Warm for hr., a t 50",20 cc. of In studies of the stability of niale fern extracts, i t clear filtrate (using a 10-cm. filter) with 26 Gm. was found that after standing 2-3 yr. there was 10% CHaOH and 2 Gm. potassium oxalate (18.4% of the loss of crude filicin, hence thc extracts were con- oxalate and 10% N KOH). After cooling, filter sidered stable for that period. Comparisons with through a dry.fi1ter (12em.) and let stand overnight bioassay methods showed little correlation of these 30 Gm. of the filtrate ( = 0.2162 Gm. opium) with with the chemical method. Flavaspidic acid, the 0.3 Gm. dinitrochlorobenzene, 5 Gm. CHaOH, and 5 most biologically active component of the extracts, Gm. water. Collect the crystals and, after suction was used as standard in the biological assays. De- is applied, wash with 3 cc. CHaOH and then with 5 termined were: The hemolytic index, the effect on cc. water. Dissolve with warming in 2 cc. 0.1 N guppies (Lebiastes reticulatus). the effect on earth- HCI, add 25 Gm. sodium chloride, dilute to 25 cc., worms (Lumbrzcus terrestis), and the effect on En- and titrate with 0.1 N NaOH using methyl red as an chytraeus albidus, Henle. There was no correlation indicator.-NEHRLICH. Deut. Apoth.-Ztg., 56,342between the chemical and the biological results on 43(1941); through Chew. Zentr.. 1941,I1 (KO. 13), earthworms or Enchytraeus, nor the hemolytic 1650. (H. M.B.) index. There was a doubtful correlation between Gallic Acid, Oxydimorphine, and Solaninethe crude filicin content and the results on the fish. Identification of. The test is carried out as follows: Such a correlation appeared t o be found initially, T o 2 cc. of pure sulfuric acid in a dry test tube add but the action upon the fish of extracts aged 3 yr. 0.01 t o 0.02 Gm. of the product, shake to effect was actually greater than the initial effect in some solution, carefully add 2 cc. of 0.1% formaldchyde itistances, despite the loss in crude filicin content.- so that i t will overlie the sulfuric acid. Callzc H. I. TOFT.Author's sumniarv of a Disbutnlion. Acid gives almost instantly a ring that is violet Cop&agen, 194G;through Arch. Pharm. Ckemi, 53, blue in the formalin layer arid grccriish blue in the 221(1946). (C. s. L.) sulfuric acid laycr. On shaking, the whole mass beFatty Acids and Esters-Colorimetric Determina- conies an intense blue. The rcaction is unaffected tion of. By using hydroxylamine hydrochloride in ovcr a temperature range of 15" to 95" (if the mixalkaline media, fatty esters form hydroxamic acids, ture is hot, the normal color apprars on cooling). easily and quickly determined colorirnetrically, The color is not destroyed by diluting with water, after adding an acidified solution of ferric perchlo- and is not dissolved in organic solvents. The reacrate. Fatty acids must first be quantitatively tion is produced only with concentrated sulfuric methylated by diazornethane or thionyl chloride in acid, not with acetic, hydrochloric or nitric acids, anhydrous ether. The basic reactions are : potassium bisulfate, etc. With 40% formaldehyde, the ring is greenish yellow aiid spreads through the R-CO*OR N€IzOH = R.CO(NHOH) ROH whole mass; with 1% formaldehyde, the ring is pink in formaldehyde and green in sulfuric acid, ( 1)

...

+

CHEMISTRY and the mixture turns brown on shaking; with 0.01% formaldehyde, the ring is blue and spreads through the whole mass. The reaction can be obServed with 2 cc. of sulfuric acid containing 25 mg. yo of gallic acid ( = 0.5 mg.) ; it will detect gallic acid in a few tenJhs of a gram of Dermatol or in tannin by ether (after rather prolonged hot hydrolysis by sulfuric acid). Oxydimorphine gives a green ring, which spreads through the mixture on shaking. The reaction is unaffected over a temperature range of 15” t o 95O. The color is not destroyed by diluting with water, and is not disolved in organic splvents. With 40% formaldehyde the ring is red in the formaldehyde layer and green in the sulfuric acid layer, and on shaking the whole mixture turns red; the transition in the color of the ring occurs with about 0.2 %formaldehyde. The reaction can detect about 0.1 mg. oaydimorphine. Sulanine gives a mauve ring (irrespective of formaldehyde concentration from 4Oy0 down t o 0.01%) which spreads through the whole mass, is not destroyed by dilution with water, and is not dissolved in organic solvents. The reaction is unaffected over a temperature range of 15” t o 95”. It can detect 0.25 mg. of solanine. All 3 reactions are still detectable with 1 cc. of O . O O l ~ o formaldehyde (0.01 mg.).P. BRETON. Ann. phurm.frang., 3 , 69-71(1945). (A. P.-C.) Gas-Absorption Apparatus-Modified. Description of an apparatus with one drawing.-A. N. BOLSTADand R. DUNBAR. Ind. Eng. Chem., (M. W. G.) Anal. Ed., 18, 337( 1946). Gas Analysis-Notes on. IV. Determination of Oxygen. For the determination of oxygen pyrogallol, yellow P, 1,2,4-trihydroxybenzene, and sodium dithionite ( NazSzO,) have been recommended. A solution containing 50 Gm. of sodium dithionite dissolved in 250 cc. of water and mixed with 40 cc. of a solution prepared by dissolving 50 Gm. of potassium hydroxide in 700 cc. of water absorbed about 97.2% of the oxygen present in 19 tests. A reagcnt prepared by dissolving 160 Gm. of potassium hydroxide in 200 cc. of water and adding 40 Gni. of triacetylhydroxyhydroquirlotle will absorb oxygen very rapidly, 5 min. being sufficient to absorb 47-190 cc. of oxygen. In ten tests, 98.17% of the oxygen taken was the average result, and combustion analysis showed that the purity was 98.5%. Very small quantities of oxygen are best determined with manganese hydroxide by Winkler’s method. Schulek showed Winkler’s titrimetric method is very accurate. Good results were obtained with oxygen in the presence of large amounts of acetylene and ethylene.-2. S w ~ and 6 I . Soos. (S. W. G.) 2. anal. Chem., 127,181-88(1944). Gas Analysis-Notes on. V. Further Applications of Pressure Method. The pressure method was applied t o t h e determination of carbon dioxide by measuring the pressure before and after the introduction of sodium hydroxide, and the average result in five determinations was 97.8% carbon dioxide. A very satisfactory method of determining combined carbon dioxide consisted in weighing out a sample, evacuating, measuring the pressure, then adding loyo sulfuric acid, and nleasuring the pressure agam. The active oxygen of hydrogen peroxide can be determined similarly by placing potassium permanganate and dilute sulfuric acid in a flask, evacuating, measuring the pressure, adding a measured volume of hydrogen peroxide, and measuring the pressure again after 5 min. The results Soos. 2. anal. Chem., 127, were excellent.-I. (S. W. G.) 188-90( 1944). Gas Analysis-Notes on. VI. Oxidimetric Application of Winkler Oxygen Determination. Leithe proposed determining oxygen by exposing ferrous hydroxide to the gas and finally detetmining the

15

unchanged ferrous hydroxide with potassium permanganate. The following procedure is preferred. By means of pipettes add 3 cc. of 32.5% pure sodium hydroxide solution and 3 cc. of 40% manganese sulfate pentahydrate solution t o the sample of gas in a glass-stoppered flask. Rotate the flask t o promote the oxygen absarption. After 15-30 min., run in 5 cc. of concentrated sulfuric acid, and shake. Then mix with 20 cc. of 0.02 Noxalic acid which also has 1.8 N sulfuric acid as preservative. Heat t o about 40” and titrate the excess oxalic acid with potassium permanganate. The rcsults agree closely with those of the iodometric Winkler procedure, as shown by 6 tests.-2. S Z A B ~ . 2. anal. Chem., 127, 192-96 (S. W. G.) (1944). Glucidic Undigestible and Intestinal Absorption Application to the Analytical Techniques of Food Chemistry. A strong criticism of the current practice of reporting “crude fiber” and “nitrogen-free extract” in food and feed analyses. Glucidic undigestible matter reduces the digestibility of other food elements. This is attributable in part to loss of endogenous nitrogen from the intestine, mechanical protection of digestible elementsfrom the action of digestive ferments, and specific action of certain demineralizing acids (phytic, oxalic) ; but is due chiefly t o the so-called “feces-forming’’ properties of glucidic uridigestible material, which produce a n increase in peristaltic activity and a reduction in the time taken by t h e food t o pass through the intestinal tract. It has been shown and confirmed that C. P. cellulose does not appreciably affect the coefficient of digestive utilization of digestible foods. It is suggested that the determination of “crude fiber” and of “nitrogen-free extract” are meaningless from a physiological standpoint, and that a more accurate and significant picture would be Qbtained by determining total reducing matter (after mild hydrolysis) and “formic acid insoluble” IGuillemet and Jacquot, Cumpt. rend. acad. scz. URSS, 216,508 (19.23) 1, the latter give a truer (though possibly not completely accurate) measure of the glucidic undigestible matter which is a much more important significant factor than crude fiber.-RAYMOND JACQUOT. Chimie 6 Zndustrie, 55, 424-30( 1946). (A. P.-C.) Glycols from the Analytical Standpoint. A brief review (with 21 references) dealing with the physical properties and the qualitative and quantitative determination (alone and in mixtures) of ethylene glycol, its ethers and esters; diethylene glycol, its ethers and esters; dioxane; propylene glycol and its esters, and butylene glyCOlS.-BERNARD GAUTHIER. Ann. pharm. franC.. 2 , 29-33, 78-81(1944). (A. P.-C.) Halides-Amperometric Titration of, Using the Rotating Platinum Electrode. Iodides, bromides, and chlorides can be successively titratcd in p i x tures with silver nitrate by using a rotating platinum electrode as the indicator electrode. For the iodide titration, ammonia is added, for the bromide titration an excess of acid is used, and gelatin is added for the chloride titration. The amprroinetric method is more rapid than the potentiometric A. method, but is not always as accurate.-H. LAITINEN, W. P. JENNINGS, and T. D. PARKS. Ind. Eng. Chem., Anal. Ed., 18,358(1946).

(M. W. G.)

Hydrocarbons-Preparation of Synthetic Samples of Low-Boiling. An apparatus is described (3 drawings) for blending low-boiling hydrocarbon\. Data are presented in the butane-pentane range.R. H. BUSEY,G. L. BARTHAUER, and A. V. METLER. Ind. Eng. Chem., Anal. Ed., 18,407-ll(1946). (M. W. G.) Hydrogen in Highly Fluorinated Hydrocarbon of. In highly fluorCompounds-Determination

PHARMACEUTICAL ABSTRACTS

16

inated hydrocarbons, like fluoroform, reaction with Light Microscopy-Polarized. The methods of sodium or 'potassium gives erratic results easily cor- determining refractive index described in this rected by using metallic magnesium.-W. H. PEAR- ,article apply t o all nonopaque materials.-PHILIP SON,et al. Ind. Eng. Chem., Anal. Ed., 18, 330 W. WEST. Chemist-Analyst.34,80(1945). (1946). (M. W. G.) (A. C.DeD.) Hydrogen Sulfide and Carbon Dioxide-SimulMethone as a Reagent for Identifying Aldehydes. taneous Determination of, in a Continuous Gas Methone (5,5-dimethyldihydroresorcinol)was conStream. A method for the simultaneous determina- densed with a series of aliphatic and aromatic altion of hydrogen sulfide and carbon dioxide in dehydes, using piperidine as a catalyst, and the natural gas is described, using iodine and barium physical constants of these derivatives are tabulated. hvdroxide solutions as titrating media.-CLYDE L. Recrystallization of the methone derivatives from B-LOHMand FRED C. RIES~NFELD. Ind. En;. aqueous alcohol containing a little HC1 caused Chem., Anal. Ed., 18, 373(1946). (M. W. G.) cyclization to give octahydroxanthenes. cu,@-Unp-Hydroxybenzoic Acid-A New Reaction for the saturated aldehydes and o-hydroxybenzaldehyde do Detection of Certain Esters of. The methyl ester not give normal derivatives with methone.-E. C. (nipagin), the propyl ester (nipasol), and the benzyl HORNINGand M. G. HORNING.J . Org. Chem., 11, (W. T. S.) ester (nipabenzyl) of p-hydroxybenzoic acid are 95-99( 1946). used as preservatives in medicinals and cosmetics. Molecular Weight Distribution Data on High m-Nitrobenzaldehyde can be used t o detect the Polymers. The author described special graph propyl and benzyl esters without saponification but papers designed t o convert molecular weight disgives a negative test with the methyl ester. T o a tribution data for high polymers into straight small sample of the ester in a test tube is added 0.5 lines.-R. F. BOYER. Ind. Eng. Chem., Anal. Ed., t o 1 cc. of freshly prepared reagent (0.1 Gm. m- 18, 342(1946). (M. W. G.) nitrobenzaldehyde in 10-cc. concentrated sulfuric Nitrogen, Phosphorus, Potassium, Calcium, and acid), noting the color in the cold and upon gently Magnesium in Plant Tissue-Determination of. A warming the tube. The propyl ester gives a red color on heating, sensitive t o 0.05 mg. of substance. scmimicro wet-digestion method developed for large number of samples. Conventional methods The benzyl ester gives a yellow color in the cold and a are used for the individual determinations.-0. J. green on heating in the presence of 0.7 mg. of ester KELLY, A. S. HUNTER,and A. J. STERGES. 2nd. and yellow-green with smaller quantities. The Eng. Chem., Anal. Ed., 18,319(1946). DESHUSSES. limit of sensitivity is 0.3 mg.-J. (M. W. G.) Pharm. Acta Helo.,20,200(1945). (M. F. W. D.) A Reagent Iodato-Argentimetric Method-Applications of. forN-Nitro-N'-2,4-Dinitrophenylurea. Amines. N-Nitro-N'-2,4-dinitrophenylureabeDetermination of silver ions by precipitation as haves as a moderately strong acid and forms salts silvcr iodate has been shown t o give accurate results. The method is here applied by an indirect with amines. It serves as a reagent for the charprocedure to determine ions which give insoluble acterization of primary and secondary amines. It is compounds with silver ions. The following general easy t o prepare, simple to use, and its derivatives technique is recommended: Place a volume (V- with amines are easy t o purify.-J. L. MCVEIGH less than 35 cc.) of sample containing X ions in a and J. D. ROSE. J . Chem. SOL,1945,621-22. (W. T. S.) flask marked a t 55 cc.,add 10 cc. N/10 silver nitrate, Organic Compounds-New Standard for Use mix, add 10 cc. M/10 potassium iodate, mix. Make up t o 55 cc., mix 1-2 min. t o agglomerate the pre- in Ultimate Analysis of, Especially Adapted for cipitate, filter on a plaited filter and collcct 50 cc. Microprocedures. The authors claim that Sof the clear filtrate representing 10/11 of the original benzylthiuronium chloride is an ideal compound for a standard in micro ultimate aiialysis since it call sample. Rcfilter the first portions of the filtratc if nccessary. To the filtrate add 5 cc. N sulfuric acid, be easily purified and it contains convcnient amounts 2-3 cc. of 5q10 potassium iodide solution, and titrate of the 5 most frequently determined elements, C, H , the liberated iodine with N/10 sodium thiosulfatc N, C1, and S.-C. L. OGGand C. 0. WILLITS. 2nd. using starch T. S. near the end of the reaction. The Eng. Chem., Anal. E d . , 18,334(1946). (M. W. G.) amount of iodine liberated represents 6 times the Palladium-Detection of, Using Pararosaniline equivalent in X ions. From the volume of thiosulfate used deduct 0.1 cc. (correction for silver Hydrochloride. p-Fuchsin reacts with palladous iodate), then add 0.1 of the total volume (correction chloride a t a mole ratio of 2 to 3, apparently forming for filtration and aliquot), and apply the following a double salt. A proposed spot test using this regeneral equation : action will detect 0.01 y of palladium at a limiting concentration of 1 part in ~~O,OOO.-PHILIPW. S. AMIS. Ind. Eng. Chem., WEST and EDWARD 'Oo0 = Total X per 1000 cc. Anal. Ed., 18,400-2(1946). (M. W. G.) 60,000 X V Oxydimorphine and the Aldehyde Function. S is thc tiormal tiiolccular cqriivaleiit of the ion Oxydimorphine i l l ronccntratrd siilfnric acid (0.01 determined. 11 is thr corrected volume of N/10 to 0.02 Gin. in 2 c c . ) sceins to hc a specific. reagent thiosulfate. 1' is thr volume of the sample taken for aldehyde functioii in acyclic, cyclic, or heterofor analysis. I )eterminations of chlorides, bromides, cyclic compounds. T o 2 c c . of reagent in a clean and iodides are discussed. Modified procedures are dry test tube add 1 cc. of a n aqueous solution of described for the determination of chlorides in aldehyde (concentration not specified, but should be urine, milk, blood, and cephalorachidic fluid.-R. sufficiently low so t h a t the color produced by sulfuric CASTAGNOU and M. DEVASLE. Bull. trav. SOC. acid alone with the aldehyde will not mask the green pharm. Bordeaux, 84,36-49( 1946). (S. W. G.) color). Chloral, benzaldehyde, o-nitrobenzaldeLead Soaps-Reaction of, with Sodium Iodide. hyde, salicylaldehyde, cinnamaldehyde, vanillin The addition of an acetone solution of sodium iodide and furfural give a green ring in the cold, a marked t o a benzene-acetone solution of a lead soap reacts green coloration when heated 3 min. in a boiling t o form lead iodide as follows: Lead soap 4-NaI+ water bath, a yellow coloratiou with violet tinge on sodium soap. The lead appears to addition of 3 cc. of water. Acetaldehyde gives in lead iodide react quantitatively and t o give a basic iodide.the cold a ring that is red above and green below, R. S. BARNETT. Ind. Eng. Chem., Anal. Ed., 18, becoming considerably intensified on heating 3 min. 333(1946). (M. W. G.) in a boiling water bath. The reaction is also given

+

CHEMISTRY by reducing sugars (glucose, lactose, maltose), sucrose, and starch (which hydrolyze rapidly in BRETON. Ann. concentrated sulfuric acid) .-P. #harm franc., 3, 72-73(1945). (A. P.-C.) Potassium Iodide-Determination of, in Liquor Iodi. When KI is determined in Liquor Iodi by the silver nitrate method of Dan. Pharm. 1933 low results are obtained. A modification of Koltoff’s method [Pharm. Weekblad, 62, 1309(1925)I was studied, using starch-iodine indicator. Method: Ten grams of Liquor Iodi is evaporated to dryness in a porcelain dish on the water bath. After heating on an asbestos wire net until no more iodine vapor is liberated, the grayish white residue weighs between 0.180 to 0.210 Gm. This residue is dissolved in 5 ml. of HzO and transferred to a 150-ml. Erlenmeyer flask. The dish is rinsed with 5 ml. H20 and then with 5 ml. of filtered starch indicator solution. The combined solutions should have a strong blue color. If not, add 1 ml. of fresh saturated aqueous solution of iodine. Two milliliters of ammonium carbonate reagent solution is added, then the fluid slowly titrated (with vigorous shaking) with 0.1 N AgNOa solution to color change to pure pale yellow. Comparisons of results obtained by a gravimetric method with those of the above titrimetric method showed that the gravimetric method had an error of not over f 1%. while the error of the titration method was a negative error of 1.52%. While a greater accuracy is obtainable using pure KI solutions without adding ammonium carbonate, the latter salt is needed t o Drevent any errors due to the presence of bromide or- chloride in the evaporaDansk tids. Farm., tion residue.-V. G. JENSEN. (C. s. L.) 20, 123(1946). Precision-Improvement of, by Repeated Measuiements. Application to Analytical Methods. By statistical means, the author examines replication of measurements as a means of increasing precision.-J. MANDEL.Ind. Eng. Chem., Anal. Ed., (M. W. G.) 18, 280( 1946). Radioactive Studies. Analytical Procedure for Measurement of Long-Lived Radioactive Sulfur, Ss6,with a Lauritzen Electroscope and Comparison of Electroscope with Special Geiger Counter. A general quantitative method for determining Sasi n tracer studies is carried out by oxidizing all sulfurcontaining samples to sulfate by the Carius procedure and subsequent precipitation as benzidine sulfate. The precipitate is specially collected and the activity is determined by either a modified Lauritzen electroscopeor a Geiger counter especially developed for soft beta-ran-F. C. HENRIOUES. TR.. . et al. Ind. Eng. Chem.,-Anal. Ed., 18,3490946j.-

.---

(M. w. .. G.)

Riboflavin-Some Optical Properties of,.’ A study of the determination of riboflavin by direct fluorophotometry [M. van Eekelen and A. Emmerie, A d a Brevia Neerland. Physiol., Pharmacol., Microbiol., 5 , 77-78( 1935)], improved by practically monochromatic excitation of fluorescenceand photographic spectrophotometric measurement of the intensity. The apparatus and technique are described in detail. Under the conditions used, most intense excitation of fluorescence was obtained with rays of the 4358 A group of mercury. It seems probable that it is the colored portion of the riboflavin molecule that fluoresces. Photochemical changes in riboflavin during exposures was always less than lo%, and decreased with the concentration. I n normal spectrum the curve of distribution of fluoresced energy had its maximum at 5135 A. The efficiency of fluorescence decreased with concentration; a t 0.025 y per cc., it was still 16.9%-of that of a solution of 1 y per cc. From a practical standpoint, with the setup described, it is quite easy to assay solutions containing 1 to 0.01 y per cc.

17

With higher concentrations trouble is encountered with irregular lighting of the spectrographic slit, due to progressive absorption of the exciting beam by the solution. With lower concentrations, solutions 4 times weaker can be assayed without difficulty, but the determination becomes inconvenient on account of the time required for exposure (36 hr., as compared with 5 hr. for solutions containing 0.01 y per cc.). Assay of complex mixtures was not included but will be studied.-MIcHEL VACHER and CLAUDINE AUSCHER.Ann. pharm. franc., 3, 64-69 (1945). (A. P.C.) Saccharin-The Colorimetry of. The following qualitative test is proposed: in a porcelain dish heat 0.01 to 0.10 Gm. of sample with 0.5 cc. of phenol Codex and 5 drops of concentrated sulfuric acid to evolution of sulfur trioxide fumes and charring of the reaction mixture, after cooling take up in 250 cc. of water, make alkaline with 10 cc. of decinormal sodium hydroxide; if saccharin is present a bright rose coloration (similar to phenolphthalein in alkaline solution) is formed. Using resorcinol instead of phenol gives a fluorescence; use of &naphthol, naphthoresorcinol, hydroquinone, or thymol does not produce any coloration. Quantitative determination: To a series of standards containing 1 to 10 mg. of saccharin add 2 drops of ferric chloride solution Codex followed by 2 drops of 20-vol. (6%) hydrogen peroxide solution; after 6 hr. (but not more than 24 hr.) measure the color in a Vanes, Bricq, and Yvon photometer using the No. 74 light green filter. and plot the standard curve with milligrams of saccharin as ordinates and photometer readings as absciassas. Determinations are carried out similarly on the ether extract, and the quantity of saccharin read directly from the curve. It is important to use 20-vol. hydrogen peroxide; stronger or weaker solutions are unsuitable. Purification of extracted saccharin: Extract the acidified sample with ether, evaporate the solvent on the water bath, take up the residue in 10 cc. of decinorma1 sulfuric acid, heat in a boiling water bath, add saturated potassium permanganate solution drop by drop to a pink coloration persisting for 2 min., decolorize by careful addition of alcohol, filter directly into a 200cc. separatory funnel graduated at 100 cc., wash with boiling water to a total volumc of 100 cc., after cooling extract with ether, evaporate the solvent, take up the residue with 3 X 3 cc. of boiling distilled water, transfer each time to a 10cc. graduate, after cooling make to 10 cc., and determine saccharin as above.-JACQUES LAVAGNE, Ann. pharm. franc., 3, 26-29(1945). (A. P.-C.) Scientific Glass Blowing and Laboratory TechSeals.-W. E. niques. VIII. Glass-to-Metal BARR and V. J. ANHORN. Instruments, 19, 344 (1946). (M. W. G.) Silver Iodate-Analytical Study of. Application to Determination of Silver Ion. Analytical characteristics of silver iodate are reviewed and its solubility and microcrystalline structure are studied. Silver ion is determined by addition of excess (5 cc.) 0.1 Mpotassium iodate t o a solution of silver nitrate (5 cc. of 2% solution), dilution to 55 cc., filtration, and iodometric determination of the excesspotassium iodate in 50 cc. of the filtrate, using 0.1 N sodium thiosulfate. The method cannot be used in the presence of acetic or nitric acids, and the reaction mixture should be nearly neutral.-R. CASTAGNOU and M. DEVASLE. Bull. traw. SOC. harm. BorW. G.) deaux, 84, 11-25( 1946). Still-Automatic Cutoff for Electrically Heated Water. Description of an apparatus with 2 drawings.-L. M. WHITE and G. E. SECOR. Ind. Eng. (M. W. G.) Chem.. Anal. Ed., 18, 332(1946). Stirring Device, Electromagnetic. Description of an apparatus with one diagram.-W. N. MC-

6.

PHARMACEUTICAL AJSTRACTS

18

Ind. Eng. &m., Anal. Ed., 18, 338 add 3 cc. of the 1 %solution of urea in acetone, shake, let stand 2 min., add 1 cc. of 0.4% dimethyl-a(1946). (M. W.G.) Sugar Acetates-Separation of, by Chromatog- naphthylamine, and compare the color as above. Total sulfonamide in blood: Neutralize 5 cc. of the raphy. The following summary is given: The chromatographic brush method with aqueous trichloroacetic acid filtrate with 10% sodium hyalkaline permanganate as brush reagent and “Mag- droxide, rcacidify with 2 cc. of 10% sulfuric acid, nesol” as adsorbent has been employed successfully make to 10 cc. with water, heat 30 min. in boiling in the separation of a selected number of two com- water, neutralize with 10% sodium hydroxide, cool, ponent (equal partions) mixtures of fully acetylated make t o exactly 10 cc., add 1 cc. of distilled water sugars and sugar alcohols. The following separa- followed by 1 cc. of 0.1% sodium nitrite, and protions were effected: P-D-glucose pentaacctate (I) ceed as above. For cerebro-spinal fluid use the from 8-maltose octaacetate (11) ; I from sucrose same method as for blood, but without the prelimioctaacetate; I from keto-D-fructose pentaacetate; nary dilution, as the sulfonamide content of the fluid Ann. I from raffinose hendccaacetate; I1 from sucrose is smaller.-R. FABREand J. HAGOPIAN. (A. P.-C.) octaacetate; I1 from rafinose hendecaacetate; raffi- pharm. franG., 2, 126-28(1944). Sulfur Dioxide-Automatic Apparatus for Denose hendecaacetate from sucrose octaacetate ; (lewo)sorbitol hexaacetate from L-rharnnitol pentaacetate. termination of Small Concentrations in Air. A The components were recovered in nearly quantita- simple countercurrent absorber is described which tive yield and in excellent purity.-W. H. Mc- absorbs water-soluble gases such as ammonia, hyNEELY,W. W. RINKLEY and M. L. WOLFROM.J . drogen chloride, and sulfur dioxide almost completely. A simple pump for transferring small (E. L. C.) Am. Chem. Soc., 67, 527(1945). D. THOMAS, Sugars-A New Reagent for the Determination of. quantities is described akO.-MOYER A new alkaline copper reagent for the determination JAMES 0. IVIE, and T. CLEON FITT. Id. Eng. of sugars is presented. The alkali in this reagent is Chem., Anal. Ed., 18,383-87(1946). (M. W. G.) Tetraiodopyrrole and Iodoform-Determination an equirnolecular mixture of dibasic and tribasic sodium phosphate. The solution contains sulfate of, in Ointments. The usual methods give low refor the protcction of cuprous oxide against re- sults. Satisfactory results are obtained by Deoxidation by atmospheric oxygen. The reagent is nigh’ method [J.plurm. ckim., 1, 131, 356(1895)] suitable for both the iodometric and the colorimetric based on conversion of the iodine t o iodic acid and technique and permits the accurate determination of iodine chloride by treatment with hydrochloric and 0.01 to 3.0 mg. of glucose or of 0.03 t o 6.0 mg. of nitric acids, treatment with sodium bisulfite, and cyanoargentimetric determination of the iodine. maltose by eithcr tcchnique.-MICIIAEL SOMOGYI. Weigh into a 500-cc. flask a n amount of ointment (F.J. S.) J . Biol. Chem., 160, 61(1945). Sulfapyridine-Analytical Properties of. A re- containing about 0.05 Gm. of the active principle, view with 15 references.-B. GAUTIIIER. Ann. add 5 cc. of nitric and 10 cc. of hydrochloric acid, heat to boiling with constant stirring for 3 min., (A. P.-C.) pharm. franG., 3, 76-SO(1945). Sulfonamides-Method of Extracting and Identi- cool completely, decant the aqueous liquid into a 10 cc. fying, in the System. The following technique in- beaker, rinse the flask with 50 cc. of water creases considerably the sensitivity of the deter- of sodium bisulfite solution, heat with stirring t o mation of sulfonamides, e.g., in urine (0.04 mg./100 liquefy the excipient, cool, and decant. To the cc. as compared with approximately 0.5 mg. by the combined aqueous liquids add 50 cc. of ammonia usual techniques). I n urine, if albumin is prcsent water, followed by 10 cc. of decinormal silver I i i treat with trichloroactic acid and filter, kccping trate, filter until the filtrate is perfectly clear, wash track of dilution. Free sulfonanzide in urine: To 1 with distilled water, wash the precipitate back into a cc. of suitably dilutcd urine (according t o the sul- beaker, add 10 cc. of ammonia water and 10 cc. of fonamide coiltent indicated by an approximate dccinornial potassium cyanide, stir t o complete preliminary determination) in a test tube add suc- solution, and titrate with decinormalsilver nitrate to cessively 9 cc. of distilled watcr, 1 cc. of 50% tri- persistent opalescence (n‘ cc.). If n = 10 - n’, chloroacetic acid solution, and 1cc. of 0.1% sodium and a is the weight of ointment, percent of tetraiodonitrite solution (prepared extemporaneously from a pyrrole = 57n/40a, per cent of iodoform =349n/300a. ~. 1% solution); shake, let stand 2 min., add 2 cc. of Direct titration of the silver in the filtrate from the 1%urea solution in acetone (dissolve 1 Grn. of urea silver iodide is liable t o give quite low results.R. G. DOURIS. Ann. #harm. franc., 2, 56-58 in 5 cc. of water and make to 100 cc. with acetone), I,A --. p - .- c.,) shake, let stand 2 rnin., add 1 CC.of 0.4% dimethyl- ( 1944). Theophylliue-Reaction of, with Gibbs’ Reagent. a-naphthylamine solution in 1: 1 alcohol-acetone mixture, shake, add 8 Gm. of ammonium sulfate The addition of a few drops of 0.4% alcoholic Gibbs’ crystals; after prolonged shaking allow the layers reagent (2,6-dichloroquinone-chloro-imide)t o a to separate, and compare the color of the upper borax or sesquicarbonate solution of theophylline layer with those of similarly treated standards con- yields a blue color. Upon the addition of solid taining 0.5 to 10.0 cc. of 0.270 solutions of the sesquicarbonate to saturation a n insoluble red-vioappropriate sulfonamides. Total sulfonainide in let precipitate is obtained.-HARRY W. RAYBIN. urine: To 5 cc. of urine add 2 cc. of sulfuric acid J. Am. Chem. SOC.,67, 1621(1945). (E. L. C.) Urea-Easy and Rapid Identification of Very (90 cc. of water sulfuric acid t o 100 cc.) and 3 cc. of distilled water, heat 30 min. in boiling water, Small Amounts of. Place a small droplet (containcool, neutralize t o litmus with 10% wt./vol. sodium ing about 0.1 mg. of urea) of 2% aqueous solution hydroxide, make t o 20, 30, 50, or 100 cc. according on a slide and warm carefully until drying is riotrd to the sulfonamide content, treat a 1-cc. aliquot as at the edge of the droplet, remove from the source indicated for free sulfonamide. From the total of heat and allow to dry in the air. Examine the sulfonamide thus found subtract free sulfonamide t o network of long, slender orthorhombic crystals. Expose the slide t o vapors from concentrated hydroobtain the combined. Free sulfonamide in blood: T o 2 cc. of blood containing 0.5 Gm. of sodium fluo- chloric acid. The hygroscopic hydrochloride forms ride add 16 cc. of 0.05% aqueous saponin solution, and liquefies. Now expose the slide t o vapors from let stand 2 min. for complete lysis, add drop by concentrated nitric acid. After several minutes drop 2 cc. of 50% trichloroacetic acid solution, let the crystalline urea nitrate can be observed. The stand 5 min., filter through paper, to 10 cc. of fil- crystals of urea can be treated directly with a trate ( = l cc. of blood) add l cc. of water and l cc. droplet of a solution containing 1 cc. of nitric acid in 10 cc. of acetone to form the crystals of urea niof 0.1% sodium nitrite solution, let stand 2 min.,

INTOSH.

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CHEMISTRY trate on spontaneous evaporation. The crystals of urea nitrate when dispersed in a droplet of sodium hypobromite solution decolorize the reagent and evolve bubbles of nitrogen visible directly or under slight magnification. T o identify urea in solid form, place several particles (less than 1 mg.) on a slide, dissolve in 1 drop of water, transfer a droplet (about of the solution) and continue as above. The solid can also be dissolved in acetone which upon spontaneous evaporation deposits characteristic crystals of urea which may then be further treated as above with hydrochloric and nitric acids. The crystals are i l l u s t r a t e d . 4 . DENIG$S. Bull. trav. SOG. phurm. Bordmw, 84, 3-6 (1946). (S. W. G.) Uronic Acids-Determination of. The distillation method for determining uronic acids has been modified by heating the sample with 19% HCI at 145' for 1.5 t o 2 hr. A simple, compact apparatus is described. Results on alginic acid were higher and more concordant than with older methods.R. M. MCCREALW.H. A. SWENSON. and W. D. MACLAY.Ind. Eng. Chem.. Anal. E d . , 18, 290 ( 1946). (M. W. G.) Viscometric Apparatus and Technique-A Photographic. Viscosity may be determined in a n Ostwald-type viscometer by photographing with a movie camera the meniscus and an electronic clock simultaneously. Times of transit may be interpolated to 0.001 SeC.-TESSE L.RILEYand GEORGE W. SEYMOUR.Ind. Eng. Chem.. Anal. Ed., 18, 387-90 ( 1946). (M. W. G.) Vitamin A-Determination of, in Liver. Vitamin A is quantitatively recovered from liver by extraction with petroleum benzin. After evaporation, the residue is taken up in chloroform and the antimony trichloride reagent applied. Errors due to soap formation, reagent impurities, and light are discussed.-W. D. GALLUPand 1. A. HOEPER. Ind. Eng. Chem., Anal. Ed., 18,28811946). (M. W. G.) Vitamin E-Chemical Determination of, in Vegetable Oils. T h e method is based on the preparation of a suitable extract of t h e oil and application of the ferric chloride and a:a'-dipyridyl color reaction. The oil is saponified with concentrated aqueous potassium hydroxide in the presence of pyrogallol, which has been shown to prevent oxidation of the vitamin E and ferric chloride-reducing substances. The u n s a p o d a b l e matter is extracted with ether and the solvent removed. The residue contains the vitamin E, carotenoid pigments and interfering reducing substances. A convenient quantity is dissolved in light petroleum, containing 1% of ethyl alcohol and subjected t o chromatographic separation using a column of activated aluminum oxide. Xanthophylls and other interfering ferric chloride-reducing substances are absorbed. while vitamin E and carotene pass through the column. The solvent from the unabsorbed portion is removed and the residue is dissolved in ethyl alcohol. I n this solution after convenient dilutions the carotene is determined b y its natural color by means of a Pulfrich photometer with the S.47 filter and the vitamin E is determined by treatment with the ferric chloride and ad-dipyridyl reagents and measurement of the color in the photometer, using the S.53 filter. From a previous determination of the a-tocopherol equivalent of &carotene under conditions identical with those of the previous determination and from a previously prepared calibration curve for a-tocopherol, the amount of a-tocopherol equivalent t o the vitamin E and the carotene, and to the carotene alone can be found, when the difference will give the amount due to vitamin E alone.3. TOSIC and T. MOORE. Biochehem. J., 39, 498 (S.W. G.) (1945). ~~

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Volatile Solvents-Determination of, in Air, Blood, and Organs. The precautions and factors which must be taken into consideration in order t o obtain significant and accurate results in the determination of alcohol, benzene, carbon disulfide, and chloroform are discussed, and techniques and apparatus are described in detail. Determination of alcohol is based on introduction of the air (preferably through a fritted glass plate) into 10 cc. of an oxidizing solution of potassium dichromate (4.262 Gm. per L.) and nitric acid, diluting with 10 cc. of water, adding 100 cc. of 1%potassium iodide solution, and titrating with decinormal sodium thiosulfate. If N = cc. required for 10 cc. of oxidizing solution and n = cc. required for titration after bubbling the air, ( N - n)1.15 = mg. of alcohol in the air sample. Benzene is determined by passing the air through a cold 1: 1 nitric-sulfuric acid mixture (which converts it into m-dinitrobenzene) , alkalinizing the reaction mixture at 30d with 50% sodium hydroxide, extracting with rectified methyl ethyl ketone, adding 1.5 cc. of 50yo sodium hydroxide t o the ketone extract, making t o definite volume (e.g., 10 cc.), letting stand 30 min. i n the dark. evaluating the violet color in a photocolorimeter, and comparing with a standard curve. The method is suitable for determining amounts of the order of 4 to 5 7 . Determination of toluene is carried out similarly, using 50% potassium instead of sodium hydroxide, as the latter does not give any coloration with dinitrotoluene. ' Determination of carbon disulfide is based on the photocolorimetric measurement of the yellow color of copper diethylthiosnlfocarbamate formed in the presence of copper acetate by the action of carbon disulfide on a n alcoholic solution of diethylamine. The absorption reagent is made by mixing 2 cc. of each of the 2 following solutions: (a) 33y0 diethylamine solution 2 cc., triethanolaniine 2 cc., 96% alcohol t o 100 cc.; (b) neutral copper acetate 0.10 Gm., acetic acid 1 drop, 96% alcohol to 100 cc. The method gives accurate results with 10 t o 250 y of carbon disulfide. For air containing 1:30,000 of carbon disulfide (0.10 mg. per L.),about 250 cc. of air gives a color suitable for measuring. Chloroform is determined by passing the air through a U-tube and a Maquenne bulb connected in series, charged with 10% alcoholic potassium hydroxide, and cooled in ice-salt mixture, refluxing the combined potassium hydroxide solutions for 10 min., evaporating on the water-bath, taking up the residue in 1 f 9 nitric acid, filtering, making up t o 10 cc., adding 1 cc. of 1% gum arabic solution, 1 cc. of 1% silver nitrate, and 1 cc. of 1 9 nitric acid, and measuring t h e turbidity nephelometrically by comparing with t h a t produced by known quantities of chloroform treated similarly. The method can determine amounts of chloroform of t h e order of 20 y with a satisfactory degree of approximation. Alcohol can be satisfactorily determined in a few drops of blood by known and proved methods (Nicloux. Widmark, Postic, Courtois, Rabat@. An apparatus for the determination of volatile solvents in blood or organs is described. It consists essentially of a tube 20 mm. in diameter, having a fritted glass plate near the bottom and a capillary tube fused through the bottom of the tube, the whole being placed in a thermostat at 50". The top of the tube is connected by means of a capillary t o the bottom of a second tube, filled with glass beads, charged with absorbing reagent, and immersed in a cooling bath. The top of the second tube is connected through a Maquenne bulb to a Jungfleisch suction regulator, which in turn is connected to a wa r suction pump. The blood is placed in the tube with a n overlying layer of l-cc. olive oil, 0.1 Gni. of sodium fluoride to prevent coagulation, and 2 cc. of 5y0 calcium stearate suspension t o prevent foaming, and air is drawn

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PHARMACEUTICAL ABSTRACTS

Androgen-Absence of, from a Diet of Natural through at the rate of 2 bubbles per second. For the determination of benzene the absorbing re- Foods. From a comparison of the standard diet of agent is I: 1sulfuric-nitric acid mixture; for tpluene, natural foodstuffs (Purina chow) with a “synthetic” fuming nitric acid; for carbon disulfide, the pre- diet in regard to its effect on the rat prostate, it is viously described diethylamine-copper acetate solu- concluded that Purina Chow does not contain aption. In the case of organs, a few Gm. of pulp are preciable amounts of orally active androgens.S. BENUAand EVELYNHOWARD. Endodiluted with 2 t o 3 cc. of oil, and the determination RICHARD (A, P.-C.) is carried out as for blood. Chloroform is deter- crinology, 38, 260(1946). mined by Nicloux’s method (Fabre, “Lecons de Antergan-Determination of, in Biological Fluids. Toxicologie,” Pt. IV, p. 74). In a raincoat factory, the benzene content of the air at the level of the Antergan is N-dimethylaminoethyl- N-benzylanirespiratory organs varied from 0.04 Gm. per cu. m. line hydrochloride. The nitroso derivative of Ana t 8:30 a. m. to 0.088 Gm. per cu. m. at 5:30 p. m. tergan gives with nitrosoresorcinol a very intense The benzene content of the blood of a man who had green coloration (probably indaniline) sufficiently been working 17 yr. in the same factory varied s eci6c t o make it suitable for the colorimetric from 0.40 mg. per L. at 8 a. m. (before starting Ltermination of Antergan, and which can be dework) t o 0.90 mg. per L a t 5:30 p. m. With a tected at a dilution of 1:800,000. To 5 cc. of An“new” subject exposed for the first time to the same tergan solution in decinormal hydrochloric acid, atmosphere, the benzene content of the blood varied add 1 or 2 drops (0.05 t o 0.10 cc.) of 1% aqueous from 0 at 8 a. m. to 0.80 mg. per L at 5:30 p. m., solution of resorcinol, shake, add 0.5 cc. of 5% soand fell again to 0 overnight. In the case of carbon dium nitrite solution, shake; in l min. there apdisulfide, fixation by the blood varied from 5 to 20 pears a fine green coloration that increases for a few mg. per L. with concentration of 0.1 to 0.2 mg. per minutes and remains stable for 3 t o 4 hr. For diluL. of air.-RhNE FABRE, et al. Ann. phurm. tions less than 1:5000 of Antergan. use 3 drops of resorcinol solution; for 1:5000 t o 1:100,000,2 drops; (A. P.-C.) f r a q . , 2, 108-15( 1944). 1:100,000 t o 1:800,000,l drop; above 1:800,000 Wines-Study on Watering of. An examination for the yellow color of the nitrosoresorcinol masks the limited t o the usual procedures for determining green color. The same reaction is obtained with 3% watering of wine can lead t o erroneous conclusions. trichlororoacetic acid instead of decinormal hydroThe various procedures are discussed and the fac- chloric acid. For quantitative determination comtors affecting the usual criteria are poipted out. pare the color with that of standards containing The value of the tartar index a s well as the deter- 1:5000 t o 1:800,000 of Antergan treated similarly mination of the ash and its alkalinity are stressed.simultaneously, and take the readings after 15 P. MESNARDand Y. BORDIER. Bull. trav. SOC. and min. The most favorable dilutions are 1:5000 to ( S . W. G.) phurm. Bordeaux, 84, 8-ll(1946). 1: 100,000. The relative error is of the order of 10%. Zinc Oxide and Bentonite in Calamine LotionIf a photocolorimeter is used, it can be standardized Determination of. The procedure for determining in the usual manner. Total Antergan can be dethe total zinc oxide in Calamine Lotion, N. F. VII, termined directly in urine (containing 0.10 Gm. or is based on the following reaction: 2K,Fe(C.N)6 more per L.) by diluting 1cc. t o 5 cc. with decinor3Znf+ = KzZns(Fe(CN)e)l 6 K + . Zinc ions In ma1 hydrochloric acid and proceeding as above. neutral or acid medium react with potassium ferro- The color of normal urine does not interfere. To cyanide t o form very slightly soluble potassium zinc determine free Antergan in urine, alkalinize 50 cc. ferrocyanide. Formerly, end point was determined of urine with 2 cc. of 20% sodium carbonate soluby means of a n external indicator but diphenylamine tion, extract twice with 25 cc. of ether, add2 cc. of alwas found to be suitable as an internal indicator. cohol to break the emulsion, extract again with 25 cc. The report gives details of procedure: reagents, of ether. If the combined ether extracts are colored sampling, assay procedure, notes about steps that wash them with 5 cc. of hundredth-normal sodium facilitate color change and makc for more accurate hydroxide, extract with 10 cc. of decinormal hydroresults, calculations, purity of ingredients, deter- chloric acid, and determine Antergan on a suitable mination of bentonite, and ferric oxide. CHARLES 0. aliquot. The method gives a recovery of 950/, and WILSONand HENRYG. SPERLINC.J. Am. I’hartii. can detect 0.02 Gm. per L. In the urine of patients Assoc., 35, 174(1946). (2. M. C.) treated with Antergan, after extraction from alkaline solution with ether and re-extraction with decinorBIOCHEMISTRY ma1 hydrochloric acid, if the test is carried out on 5 cc. of the undiluted hydrochloric acid extract, Acetyl-dl-tryptophane, Non-utilization of, Intra- before appearance of the green color there develops venously Administered. Acetyl-dl-tryptophane in a slight yellow coloration which modifies the green aqueous solutions was administered intravenously color. The yellow color is not prevented by washto 3 human subjects. Seventy t o 83% of the ad- ing the ether with dilute sodium hydroxide, and is ministered substance was excreted unchanged, al- not given by the urine of the same patients before most all wifhin the first 6 hr. The excreted material treatment with Antergan, indicating t h a t i t is due to was racemic; there was no preference utilization some other product excreted in the urine. Correct of the ~-components.-JAMEs MURRAYLUCK,PAUL results are obtained by measuring the color it1 DELOSBOYER,and VICTORE. HALL. Proc. Soc. monochromatic light, e.g.. with a Verncs photomc(A. E. M.) Exptl. Biol. ,Wed., 62, 177(1946). ter, a Hellige panphotometer, or a Meunier photoAmino Acid Feeding-Influence of, upon Anti- colorimeter. Determination of Antergan in Blood. body Production in the Protein-Depleted Rat. Collect 5 cc. of blood in 35 cc. of 0.05% saponin, let Antibody production depends on an adequate sup- stand 5 min., add 10 cc. of 15%trichloroacetic acid, ply of essential amino acids coming either from food mix, let stand 5 min., and filter. For total Antergan, or the animal’s own protein stores. When both t o 5 cc. of filtrate ( = 0.5 cc. of blood) add 1 cc. of sources are deficient the antibody producing ca- 1%resorcinol solution, shake, add 0.2 cc. 5% sopacity is markedly diminished. This capacity is re- dium nitrite, shake, let stand 15 min., and compare established by feeding balanced quantities of with standard solutions. For free Antergan, make amino acids coming from food protein, enzymatic the trichloroacetic acid filtrate alkaline with sodium or potassium bicarbonate, extract with ether, exprotein hydrolyzates or amino acid mixtures.and tract the ether solution with decinormal hydroROBERTW. WISSLER,ROBERTL. WOOLRIDOE, C. HAROLD STEFFEE.Proc. SOC.Exptl. Biol.Med., chloric acid, and determine as for total Antergan. (A. E. M.) There is no interfering yellow color such as is pro62, 199(1946).

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CHEMISTRY

duced in t h e case of urine. Taking 30 cc. of a t r a t e ( = 3 cc. of blood) as little as 0.2 mg./100 cc. of blood can be determined. The same technique is applicable to milk. Tests on humans and on animals showed t h a t only 10 t o 20% of the injected or ingested dose is recovered in t h e urine, indicating transformation of the product in the system. Elimination of a single dose is usually practically complete after 24 hr. The maximum blood concentration cccurs 4 hr. after administration and is of the order of 1 mg./100 cc.-P. DUFJOST.Ann. pharm. frunG., 1, 145-48(1943). (A. P.-C.) Antibiotics-The Mechanism of Action of. The Reaction of Unsaturated Lactones with Cysteine and Related Compounds. Reaction of cystine and related aminothiol derivatives has been investigated and appears t o proceed through addition of the thiol group t o the double bond, followed in the case of the #a-butenolides by reaction of the lactone with the amino group and loss of water. A &substitution in both the A 4 - and A&r-butenolide series prevents reaction with cysteine. These reactions may be of significance as indicating a possible mode of action of unsaturated lactone antibiotics with sulfhydryl and possibly amino groups of enzyme prOteinS.-cHESTER J. CAVALLlTO and TE~EODORE H. HASKELL.J. Am. Chem. Soc., 67, 1991(1945). (E. L. C.) Barbiturate in Urine-Rapid Detection of. For the rapid confirmation of suspected barbiturate poisoning the method of Griffon and Breton, for the detection of barbiturates in urine, is reconimended. In this method the urine is absorbed by anhydrous sodium sulfate and the mixture packed in a tube over a layer of vegetable charcoal and a layer of magnesium oxide and the barbiturate is extracted by percolation with ether. The percolate is collected in a warmed receiver so t h a t evaporation of the ether is instantaneous. Parri’s reagent, cobalt nitrate and diethylamine in alcohol solutions, is used t o detect the barbiturate in the residue. The whole operation can be completed in an hour. The presence of phenobarbital is readily detected in the urine of a person receiving a dose of 0.2 Gm. of the barbiturate. T h e present authors confirm t h a t the method is sensitive t o 0.2 mg. in 20 cc. of urine.X. DENISand A. LAMBRECHTS. Rev. belge sci. m a . , 9, 247(1940); through Quart. J. Phurm. Phurmacol., 19, 199(1946). (S. W. G.) Benzylidene-AcetoneDetection and Determination of, in Revulsives. T o 50 Gm. of a revulsive containing, e.g., 0.20 Gm. of benzylidene-acetone. add a slight excess (0.35 Gm.) of Girard and Sandulesco’s reagent T (trimethyl acethydrazide ammonium chloride (CH8)aN(C1)CHzCONHNH2). followed by 20 cc. of absolute alcohol and 2 cc. of acetic acid, r d u x for 40 min., cool, pour into 100 cc. of ice water, add sodium hydroxide t o neutralize about 90% of the acidity (avoiding reaching the bromothymol blue end point) (the alcohol content of the dilution should be 10 t o 20%), decant t h e aqueous solution and separate t h e terpenes by 3 extractions with ether, to t h e aqueous solution add sufficient concentrated hydrochloric acid (about 7 cc.) to bring the acidity t o about half-normal, to normal, let stand 1 t o 2 hr., wash the combined ether extracts with water, dry with anhydrous sodium sulfate, and distil into a tared flask. Yields of 70% to7570areobtained. The benzylidene-acetone thus isolated can be identified by : ( 1) solution in concentrated sulfuric acid which gives a deep red coloration; (2) Legal’s reaction: (a) dissolve a few 0.01 Gm. in 1 cc. of alcohol, add 1 cc. of extemporaneously prepared, approximately 5% sodium nitroprusside solution, followed by 1 or 2 drops of sodium hydroxide solution, and acidify with acetic acid; a n intense blue coloration is produced that is

21

not destroyed by dilution; (b) dissolve a few 0.01 Grn. of benzylidene-acetone in 1 cc. of alcohol, add bromine water with shaking t o a persistent slight coloration, add 1 cc. of sodium nitroprusside, make alkaline with sodium hydroxide, and acidify with acetic acid; a violet color is produced; (3) by formation of the oxime, melting point 110O.MARC CHAMBON.Ann. pharm. frun ., 2, 98-99 (1944). [A. P.-C.) Carbohydrate Metabolism in Normal Pregnancy. %rial glucose-tolerance tests were done on 25 nor ma1 pregnant patients, a t each trimester, immediately after delivery and several months post partum. The fasting blood sugar values were! well within normal limits. The peaks, too, were normal except in rare cases. The 2-hr. levels during pregnancy were abnormally high in a large percentage of cases (81%). For this reason, a high 2-hr. level cannot be considered diagnositic of diabetes during pregnancy. On the other hand, the 3-hr. level was normal during pregnancy with one exception and thus may be more properly used as a criterion. The incidence of high 2-hr.values persisted immediately after delivery but dropped sharply after the puerperium. These findings indicate a n adverse effect of pregnancy on carbohydrate metabolism. Pregnancy glycosuria is probably due t o a high alimentary hyperglycemia rather than to a loxering of’the renal threshold.-D. HuRwrTz and D. JENSEN. New Engl. J. Med., 234, 327(1946). (W. H. H.) Chloride, Carbonic Anhydrase, and Catalase in t h e Tissues of the Perch (Perca Flavescens Mitchill). Chloride, carbonic anhydrase, and catalase were determined in t h e swimbladder, liver, muscle, brain, and stomach of the perch (Percu pavescens). All superficial blood was removed from the tissues, but no correction was made for blood or for extracellular fluid contained in the tissues. The average chloride content found (in milliequivalents per Kg.) was swimbladder 88, liver 42, muscle 24, brain 43, stomach 7. Carbonic anhydrase activity (in units per Gm.) was found t o be swimbladder 47, liver 119, muscle 78, brain 707, stomach 207. Catalase activity (in cu. mm. of oxygen per mg. evolved after 1 rnin. at normal temperature and pressure) was swimbladder 7, liver 108, muscle 1.3, brain 4.VIRGINIA S. BLACK. Rev. can. b i d . , 5, 311-18 (1946) (in English). (A. P.-C.) Choliaestera6e-Wbiting Alkaloids-D etection of (Particularly Eserine). The atlthors made a systematic investigation of the anticholinesterase activity of some 40 alkaloids (Bull. SOC. chim.biol., 25, 1353+32(1943)). Eserine was found t o be by far the most active: At a concentration of 10-6 it produces a 90% inhibition of the hydrolysis of acetylcholine by horse serum; at the same concentration geneserine produces a 60% inhibition, and with the other alkaloids studied the inhibition did not exceed 20% t o 30y0. On the basis of these findings a method is proposed (technique described in detail) for the toxicolcgical detection and approximate quantitative determination of eserine. It consists essentially in dissolving t o known concentration or 10-3 the alkaloidal residue obtained by known extraction and purification methods and measuring a t 5-min. intervals its action on the liberation of acetic acid from acetylcholine by horse serum at 37’ (cf. Vincent and Maugein, Bull. sci. phurmacol., 49, 141-45(1942)). The method could be used also t o obtain some idea of t h e nature of an alkaloidal residue on the following general basis : Eserine gives 90% inhibition a t a concentration of 10-8; geneserine gives the same inhibition at a concentration of 10-4. At this same concentration pelletierine, ibogaine, and conicine give 85% inhibition; colchicine, strychnine and ergotinine give

22

PE~ARMACEUTICAL ABSTRACTS

75T0 t o 85y0; quinidine. papaverine. sparteine, quinine. emetine. and cocaine give 60% to 75%; ergobasine, thebaine, hyoscyamine, ergotamme, and veratrine give 45% t o 60%; narcotine, narceine, brucine, and hordenine give 3070 to 40%; ephedrine, atropine, morphine, dionine, yohimbine, and apomorphine give 20’3; to 3070. The method may be of some use for helping to identify other alkaloids; but it is only in the case of eserine that it can identify positively and determine quantitatively microquantities.-D. VINCENTarid P. BEAUJARD.Ann. phurm. franc.. 3, 22-26(1945). (A. P.-C.) Enzymatic Oxidation in Ciliary Processes. The epithelium of the ciliary processes was decomposed by mechanical agitation and the granular cell debris was collected for study. Marked differences were found in the enzymatic activities and in the chemical composition of the successively separated fractions of cell debris. The fractions with the lowest content of lipoids and of nonextractable phosphorus show the lowest ratio of the oxidation rate of hydkoquinone t o that of succinate. The fractions with the highest concentration of lipoids and of unextractable phosphorus show the highest ratio.-H. HERRMANN, J. S. FRIEDENWALD, and M. B. Boss. Bull. Johns Hopkins Hosp., 78, 119(1946). (W. H. H.) Folic Acid-Purified Rations and the Importance of, in Mink Nutrition. Feeding minks highly purified, vitamin B complex free rations of varying protein levels supplemented with thiamine, riboflavin, niacin, pyridoxin, pantothenic acid, and choline produced a severe deficiency in 10 to 13 wk. The administration of synthetic folic acid a t the time of severe deficiency symptoms resulted in an immediate recovery whereas controls without folic acid died. There seems t o be present in the liver another factor distinct from known vitamins which is necessary for body weight and hemoglobinregeneraE. SCHAEFER, C. K. WHITEHAIR,and tion.-A. A. C. ELVEHJEM. Proc. SOC.Exptl. Biol. Med., 62, 169(1946). (A.E.M.) . Galactose Removal Constant. A series of determinations pertaining t d liver functions were performed simultaneously with the galactose test on all patients. These included serum protein partitions, serum bilirubin, plasma prothrombin, cephalin cholesterol flocculation, bromosulphalein dye retention, and urinary urobilinogen excretion. There was a good correlation between the values of galactose removal constant and the other liver function tests.-H. COLCHER, A. J. PATEK,JR., and F. E. KENDALL. Bull. N. Y . Acad. Med., 22, 479(1946). (W. H. H.) Hemoglobin Determination-Artificial Standard for. Haemin, which has been suggested as a standard substance in the colorimetric determination of hemoglobin, has been found t o be unsatisfactory. Some samples yield a color intensity greater than that calculated from the iron content, the solution changes color on keeping and not only does the absorption spectrum differ from that of blood but the spectra of individual hamins differ from one another. A standard containing chromium sulfate, cobalt sulfate, and potassium dichromate is proposed, which is stable, reproducible and follows the absorption wectrum of blood in N/10 sodium hydroxide between the yellow and blue-green regions. The standard is prepared by dissolving 11.61 Gm. of potassium h o m e alum, 13.10 Gm. of freshly dried anhydrous cobalt sulfate and 0.690 Gm. of potassium dichromate in water, adding 1.8 cc. of N/1 sulfuric acid, heating to boiling for a minute, cooling, and diluting to 1L. A more precise method is t o use a solution of 3.42 Gm. of potassium dichromate, completely reduced by means of sulfur dioxide, in place of the chrome alum. Tne. hemoglobin

equivalent of the standard as determined in the Hilger absorptiometer was in close agreement with the value obtained with a visual colorimeter in natural and artificial light, both with and without green filters. Based on the oxygen capacity, the equivalent was found t o be 15.6 * 0.2 Gm. of hemoglobin per 100 cc. of blood and 16.0 * 0.2 Gm. when based on iron content. During this investigation evidence was obtained indicating the presence of “inactive” iron in normal male blood, since the iron content of some 10 samples was 5% higher than that equivalent t o the oxygen capacity.-Q. H. GIBSONand D. C. HARRISON. Biochem. J.. 39, 490( 1945). ( S . W. G.) HistamineBioassay of, in Organic Fluids. The method is based on the pharmacological action of an extract as compared with that of a known quantity of histamine. Preparation of the extracf: Collect 10 cc. of blood in 15cc. of acetic acid, shake, let stand 1 hr., filter. wash, to the histamine-containing filtrate add 10 cc. of concentrated hydrochloric acid, boil gently for 1.5 hr., evaporate to about 5 cc., add 10 cc. of alcohol, evaporate t o dryness on the water bath, repeat the operation 3 times, take up in 3 cc. of distilled water, neutralize with a few tenths of a cc. of fifth-normal sodium hydroxide, and make t o the original volume with distilled water. Preparation of the intestine: Take the last 2 cm. of the small intestine of a n adult guinea pig which was killed by bleeding, preferably fasting since 5 hr., place in warm Tyrode’s solution, completely remove the insertion of the mesentery, mount in an isotonic myograph filled with Tyrode’s solution through which is passed a current of oxygen or air, place in a thermostat at 34”. let stand a t rest for 30 min. during which the Tyrode’s solution is changed 2 or 3 times, feel out the sensitivity to constant volumes of progressively increasing doses of standard solutions of histamine; if it is suitable (appreciable response t o 0.05 y in 5 cc.), the determination can be started. Determination: Record on a slowly rotating cylinder the contraction of the intestine produced by adding alternately t o the bath 0.5 or 1.0 cc. of t h e extract (or a smaller volume brought t o uniform volume by addition of Tyrode’s solution) and a known quantity of histamine dissolved in the same volume, until the action of the extract can be fitted fairly closely between 2 contractions produced by known amounts of histamine.+. L. PARROT and G. RICAET. Ann. biol. clin. 2 , 129-34(1944) ; through Chimie 6 In(A. P.-C.) dustrie 53, 393( 1945). Histamine-Role and Determination of. A brief review of the Dhvsiolodcal role and the chemical and biological det&inati& of histamine.-B. GLASSON. Schweiz. Afioth.-Ztg., 83, 725-.27(1945). (M. F. W. D.) Insulin: Its Chemistry and Physiology. A.review with 130 references from which i t is concluded that insulin exhibits all the properties of a typical protein. On the evidence at present available, it must be assumed t h a t the physiological activity of insulin is a specific property of the whole protein molecule. The following physiological functions may be attributed t o insulin: (1) Acceleration of glucose oxidation in the tissues. (2) Increase in the rate at which glucose is converted to glycogen and possibly fat in the muscle and in other tissues. I t is still undetermined whether insulin has a direct influence on the formation of liver glycogen or whether i t inhibits hepatic glycogenolysis which is caused by certain other hormones. This inhibitory effect of insulin would enable the liver of the normal animal t o retain its glycogen, and would also account for the disappearance of liver glycogen in the depancreatized animal (absence of insulin). Increase in glucose oxidation and in the rate of glycogen formation probably accounts for the fall in blood

CHEMISTRY sugar observed after insulin injection. (3) Inhibition of carbohydrate formation in the liver from noncarbohydrate sources. Gluconeogenesis is under the partial control of certain other endocrine principles (anterior pituitary and adrenal cortex). (4) Inhibition of excessive formation of ketones. Decrease in glucose oxidation and increase in hepatic glycogenolysis and gluconeogenesis cause hyperglycemia, which may be due t o t h e following factors: (a) deficient supply of insulin; (b) liberation, either at a normal or excessive rate, of those principles which enhance glycogenolysis and gluconeogenesis and of those which reduce glucose utilization. -H. JENSEN. Rev. can. biol., 5, 281-310(1946) (in English). (A. P.-C.) Intravenous Glucose-Tolerance Test in Liver Disease. An intravenous glucose-tolerance test was performed on 25 patients with liver disease, each of whom showed by clinical and laboratory examinations evidence of severe to moderate liver damage a t the time the test was performed. Although extreme variations appeared in individual tests, by far the greater proportion of the values obtained were within normal range. No diagnostic value could be assigned t o the tests in this series as an index either t o liver function or t o disturbed carboand H. J. hydrate metabolism.-J. A. CAMPBELL TAGNON.New Engl. J. Med., 234, 216(1946). (W. H. H.) Methionine-Failure of, to Reduce Nitrogen Loss in Postoperative Herniorrhaphy Patients on Restricted Diet. The administration of 6 Gm. methionine daily to men receiving a low caloric diet failed to show a protein sparing action as concluded from the urinarv excretion of nitroeen.-CEcILxA RIEGEL, C. E. KOOPand R. P. G ~ G G E R Proc. . SOG.Exfitl. Bwl. Med., 62, 7(1946). (A. E. M.) ,8-Methyl-d-Glucoside-Bi$e&cal Synthesis of, in Dioxane Medium. Addtion of 2.0 Gm. of finely powdered almond emulsin t o a mixture of aqueous 20% (weight in volume) glucose solution 40 parts, pure commercial methanol 120 parts, redistilled pure commercial dioxane t o 400 parts, resulted in the gradual disappearance of the glucose and formation of @-methyl-d-glucoside,showing that this biochemical synthesis can be carried out with excellent yield in slightly aqueous dioxane medium.-H. HBRISSEY and P. FLEURY. Ann. phnrm. franc., 3, 57-58(1945). (A. P.-C.) Micro-Biological Assays-Design and Statistical Analysis of. In many types of micro-biological assay, the measured response is found t o be linearly related to the dose, and not t o the logarithm of the dose as is usual in macro-biological assays. If the linear relationship extends down to zero dose (and, by a simple modification in the basal medium, this can always be ensured) the most precise assay of a test preparation against a standard preparation would be obtained by using only 3 groups of tubes, one at zero dose and the others a t the highest doses of the 2 preparations that could be given without risk of exceeding the upper limit of linearity. Such an assay design is considerably more efficient than a 4-point design, with 2 doses of each preparation, analogous t o that frequently used in macro-biologicai work. This common-zero 3-point design, however, is not in practice, suitable for assays, since it provides no data for the detection of departures from linearity, the occurrence of which would indicate ,either that the form of statistical analysis used in truly linear assays was in this case inappropriate or that by reason of faults in the experimental technique the assay was invalid. If the validity of the assay and of the statistical analysis is t o be examined, intermediate dose levels must be included, in spite of the consequent reduction in the precision with which the potency is estimated for a fixed total

23

number of observations. A design which gives a reasonably sensitive test of validity without too great a sacrfice of efficiency, and also has the merit of being extremely convenient in practice, is that which has equaI numbers of tubes at 5 levels, those used in the 3-point assay together with half-doses of each preparation. Whatever design is used, the distribution of tubes between the doses of the test preparation should be the same as for the standard, but there are other 5-point designs co,nforming to this condition which may occasionally be useful. In this paper formulas have been given, applicable t o the general common-zero &point design, for estimating the potency and its standard error, for testing the validity of the assay, and for assessing the efficiency of these estimations and tests relative to the best that could be obtained with a specified total number of tubes. Designs involving a greater number of dose levels may be required by research workers. General formulas for deriving the estimate of potency from such designs have been given, together with the simpler forms of these expressions appropriate t o a symmetrical common-zero (2k 1)-point design. Special reference has been made t o the symmetrical 9-point design, which is fairly convenient in practice and would be useful if in some special case there was reason t o suspect the occurrence of deviations from linearity of a sigmoid nature in the response curves. Finally, the method of setting out the calculations in the form of an analysis of variance has been demonstrated.-E. C. WOODand D. J. FINNEY.Quart. J. Phurm Phurmcol , 19, 112-27( 1946). (S. W. G.) Nicotinamide-Biosynthesis of, in Man. Four subjects subsisted for 3 mo. on a diet supplying a daily intake of 1.5-2 mg. nicotinamide without showing any signs of deficiency. Since the urinary excretion of N-methylnicotinamide showed no reduction, it is concluded that nicotinamide is synthesized by intestinal bacteria. Sulfasuccidine does not interfere with this synthesis from which is concluded t h a t the bacteria in question are not affected b y this drUg.-vICTOR A. NAJJAR, et al. Proc. SOC.Exptl. Biol. Med., 61, 271(1946). (A. E. M.) Nicotinamide, Nicotinic Acid, and Diethylamide of Nicotinic Acid (Coramine)-Metabolism of, by Newborn and Premature Infants. The elimination of nicotinamide methochloride b y newborn infants was determined in normal conditions and following the administration of nicotinamide, nicotinic acid, and coramine. Nicotinamide was found t o be most active, followed by nicotinic acid and then coramine. Premature infants eliminated less nicotinamide methochloride than normal newborn infants under the same conditions. Evidence is presented that coramine is normally converted into nicotinamide methochloride. Methionine had little or no effect on the methylation of the nicotinamide.-R. A. COULSON and C. A. STEWART. Proc. SOC.Exptl. Biol. Med., 61, 364(1946). (A. E. M.) Nitrogen Metabolism-Importance of Autoregulation in. In the light of the data presented the mechanism of autoregulation is apparently the following: When there is a n increased quantity of nitrogen metabolites in the blood there is a reduction in the disintegration of protein in the tissues. As a result of the surplus production of the hormones of protein metabolism of the hypophysis, synthetic processes become active in the nitrogen metabolism. All this leads t o a reduction of the increased concentration of nitrogen metabolites in the blood and t o the reduction of the azotemia t o norm$. This new law provides for a new method of dietetics and for the functional diagnosis of diseases in which orotein metabolism is disturbed.-% M. L s ~ ~ s . 'Byit. Med. J., 4457, 876(1946). (W. H. H.)

+

24

PHARMACEUTICAL ABSTRACTS

Nitro russide Reaction for the Determination of I(etone%odies in Urine; Assessment of the Value. The nitroprusside reaction is a reliable test for urinary ketones; with an understanding of the limitations and underlying chemistry it can be used as a roughly quantitative method of determining the degree of ketosis. Neither the literature nor the current textbooks and manuals adequately describe the reaction. The literature is reviewed and the mechanism of the reaction is described. Data are given for the sensitivity of the LeNobel, Rantzman, Ross, Lange, and Rothera tests. It is shown that the sensitivity of the various tests is determined largely by the concentration of ammonium salts. Three methods are recommended: the LeNobel test which is the least sensitive, the Ross test which possesses intermediate sensitivity, and the Rothera test which is the most sensitive. These procedures are described briefly. The tests should be carried out only on the freshly collected sample. They then determine acetoacetate. Fresh urine contains relatively little acetone. The rate of excretion. not the concentration, of acetoacetate and j3-hydroxybutyrate is important. The quantity of acids excreted is fairly constant in a given period of time, and is not markedly affected by the urinary volume. The relative quantity of j3-hydroxybutyrate is a logarithmic function of the rate of excretion of acetoacetate. Within the range of concentrations of acetoacetate detected by the Rothera and LeNobel tests, from 50% to 75% of the total acetone bodies is present as acetoacetate. With this knowledge, and with the information gained from the use of any 2 of the 3 nitroprusside tests, it is possible t o calculate the approximate rate of excretion of total acetone bodies. A positive nitroprusside test does not necessarily indicate insufficient metabolism of carbohydrate The conditions leading t o excretion of acetoacetate above the normal levels are discussed.T. E. FRIEDEMANN, B. B. SHEFT,and V. C. MILLER. Quart. Bull. Northwestern Univ. Med. School, 20, 301( 1946). (W. H. H.) “Nostras” Gum-Mycolysis of a, by Some Ligneous Fungi. According t o F. T. Brooks [ N e w Phytulogist, 27, 85-97( 1928)], in “lead disease” of plum trees caused b y Stereum pzrrpureum the action of the parasite results in the formation of a quantity of gum that is such as t o act as an impassable barrier through which the fungus cannot pass, and the tree is thereby saved. The action in vitro of Stereum purpurcum, Xantluhrous hispidus, Polyporus sulfurcus, Coriolus versicolor, and Asterula gummipar Vuill. (isolated from trunks of Acacia uerek from Mauritania) was studied on cherry tree gum. I n 3 mo. A . gummi@ra liquefied the gum completely with formation of reducing sugars. S. purpureum showed a marked, though considerably lower, lytic activitv. The other orwnisms tested showed little or no iuch activity.-L.-LuTz. Ann. phurm. franc., 3, 9-lO(1945). (A. P.-C.) Palmar Sweat-Chemistry of. A preliminary report on the apparatus and techniques employed in the study of the chemistry of palmar sweat is made. The studies were made on normal persons and patients suffering from atopic dermatitis. Results show the sweat glands to be more efficient in the excretion of sodium chloride than previously suspected. The PH of such sweat was found t o vary from 5.2 t o 6.75 and is not consistantly correlated with the urinary pH. Patients having atopic dermatitis have, on the average, slightly lower pH, excrete a larger volume of sweat, and the sweat has a lower chloride concentration.-W. C. LOBITZand A. E. OSTBRBERG. J . Investigative Dermatol.. 6 , 63 (1945). (M. W. G.) Paludrine-Estimation of, in Bloqd. Paludrine (N-9-chlor-phenyl-N-isopropylbiguanldine) is one

of a series of chemically related drugs which have been shown t o possess considerable antimalarial activity. Estimations have been carried out by the method described in parallel with the diazo-method of Spinks and Tottey. Agreement between the methods has been good. The mean concentration found in a series of blood samples from volunteers taking paludrine was 48 ?/lo0 ml. estimated by the dye method, and 47 ?/lo0 ml. by the diazo method. The standard error of the difference amounted to 15 ?/lo0 ml. This is small enough to be unimportant in clinical use.-E. J. KING. Lancet 250, 886 (1946). (W. H. H.) Pantothenic Acid Deficiency-Chemical Cytology of the Rat’s Adrenal Cortex in. Weanling male rats placed on a purified diet deficient in pantothenic acid grew poorly in comparison t o their controls and presented other symptoms commonly described for this deficiency. Moreover their adrenal cortices became relatively large and the zonae reticularis and fasciculata were progressively drained of ketosteroids and gave cytological evidence of exhaustion. By the end of 6 wk. the zona fasciculata was entirely depleted of its hormone. Wile there was no apparent significant alterations in blood glucose and nonprotein nitrogen, the severely deficient animals exhibited a decrease in liver glycogen as well as shrunken and, often, dying liver cells. After the 4th week of the deficiency the kidney tubule cells near the medulla likewise showed signs of degeneration. The thymuses of the deficient rats were atrophied in comparison with those of the controls. All of these symptoms are interpreted as indications that a pantothenic acid deficiency acts as an “alarming agent” for the rat. Such agents cause the release of pituitary adrenotropin which stimulates the adrenal t o enlarge and increase its secretion of corticosterone. A deficiency of pantothenic acid is so severe an “alarming agent” that the adrenal becomes exhausted of corticosterone. The livers of the control animals exhibited a transitory fatty infiltration which is tentatively attributed t o a deficiency of certain water-soluble vitamins ordinarily provided by bacterial synthesis in the inteStine.-HELEN WENDLERDEANEand JOHN M. MCKIBBIN. Endocrinology, 38,38MOO(1946). (A. P.-C.) Pantothenic Acid-Growth Inhibition by Analogs of. m. N-Pantoylalkylamines and Related Compounds. The preparation and physiological properties of a series of dl-N-pantoylalkylamines and of dl-N-pantoyl-j3-methoxyethylamine, dl- N-pantoyl-B-phenylethylamine,dl-pantothenonitrile, and dl-pantothenylamine are reported. All of these compounds inhibit growth of various organisms which require pantothenic acid; the inhibition is competitive in nature, and is specifically alleviated by excess pantothenic acid. The compounds vary markedly in inhibitory properties for a single organism; similarly, the relative potencies of members of a series of compounds differ markedly for different organisms.-WrLLIAM SHIVEand ESMONDE. SNELL.J . Biol. Chem., 160, 287 (1945). (F. J. S.) Pregnancy-Use of South African Frog in the Diagnosis of. The extrusion of eggs by the South African clawed frog on stimulation by mammalian gonadotropic hormones offers a test for pregnancy. Among its advantages are speed, since ordinarily only 8t o 12 hr. are required for a positive reaction; ease in the performance and reading of the test; economy, since the animals can be reused over a period of many years; and simplicity in feeding and maintenance of the animals, since they require no elaborate or separate animal rooms. I n a carefully controlled series of 100 consecutive routine urine analyses, the test gave no false-positive reactions, but in 4 cases of

CHEMISTRY

25

low-titer uriiies it failed to give a positive reaction. aniiiiation of a number of blood samples showed that I t is believed that with minor modifications in the there is no appreciable difference between the ribooriginal technique these false-negative reactions flavin contents of normal and rheumatic blood; furcan be avoided and that this test can be made t o thermore, no correlation of the riboflavin content compare favorably with the older, more widely ac- with the sedimentation of rheumatic blood was poscepted rabbit, rat, and mouse tests. The rapid sible. The presence of a substance in blood which diagnosis that i t affords is desirable in general, and causes interference with the assay is reported.and H. COKE. Biochem.J.,39, in cases presenting difficult diagnostic problems this E. A. M. BRADFORD factor may be of great valueain indicating the correct 379( 1945). ( S . W. G.) therapeutic procedure t o be adopted.-S. L. ROBSerum Amylase and Serum Lipase in Mumps. BINS, F. PARKER,and W. C. DOYLE. New Engl. Serum amylase determinations are of value in the J. Med., 234, 784( 1946). (W. H. H.) differential diagnosis of parotitis. Ninety-six per Proteins-Relative Efficiency of the, in Polished cent of 224 patients with mumps showed elevations Rice and in Enriched Wheat Flour. Feeding experi- . of serum amylase in the course of the disease. 111 ments showed t h a t on the same plane of protein the first week of disease 84% of the mumps patients intake animals on proteins of polished rice gained showed elevations of serum amylase. This peralmost 4 times as much as those on enriched wheat centage fell progressively week b y week so that in flour.' The efficiency of proteins in polished rice the 4th wk. (actually 22-32 days) 27.5% of patients was 158% ereater than those in the Droteins of wheat still showed elevated values of serum amylasc. flOUr.-BXGNETT SURE. P r O C : sic. fiptE. Biol. Elevations of serum amylase apparently follow the Med., 61, 342(1946). (A. E. M.) evolution of the parotitis. The appearance of orProteins of Leguminosae Seeds (Fabism, Phas- chitis and epididymitis as complications of mumps ism, Lathyrism)-Intolerance to and Food Poisoning does not affect the amylase of the serum. Hence in by. A review with 18 references.-F. ROTABAand apparently primary acute orchitis or epididymitis P. B R U ~ R E Ann. . pharm. franc., 2, 104-7(1944). of mumps origin, the elevation of serum amylase will depend upon how soon the orchitis and epididy(A. P.-C.) Prothrombm-Components of. Undccalcified mitis follow the original parotitis (which may have hemophilic plasma shows markedly less loss of been overlooked by the patient or missed by the prothrombin activity on storage than does oxalated examiner). In true primary orchitis and epididymiplasma. Aluminum hydroxide removcs compo- tis of systemic mumps origin unassociated with nent R from native hemophilic plasma. The pro- parotitis, normal values of serum amylase may be longed prothrombin time in stored plasma is strik- anticipated. Elevated serum amylase found uningly shortened by the addition of defibrinated complicated mumps is extrapancreatic in origin. plasma treated with aluminum hydroxide. De- Eighty-nine and one-half per cent of 224 mumps layed prothrombin time in preserved plasma is not patients had normal serum lipase values; 11.5% due t o alterations in the fibrinogen.-ARMAND J. of patients had slightly elevated values. None was QUICK. Proc. SOC. Exptl. Biol. Med., 62, 249 greater than 1.25 cc. of N/20 NaOH and none showed any clinical evidence of pancreatitk(1946). (A. E. M.) Protoporphyrin. The following method of prepa- S. CANDELand M. C. WKEELOCR. Ann, Internal (S. W. G . ) ration was used: Mix clotted human blood with an Med., 25, 88-96(1946). Soya Bean Trypsin-Inhibitor-Anticoagulant Acequal volume of HCI and heat to looo until all clots are broken up. Cool and add 3 vol. of watcr. tion of. Crystalline soya-bean trypsin-inhibitor Extract with 1.5 vol. of chloroform and wash the appears t o be a potent anti-thrombokinase, with a chloroform with water until neutral. Extract the slight inhibitory effect on thrombin. A sample of chloroform solution with '/e vol. of N/20 NaOH, crystalline pancreatic trypsin-inhibitor had a similar acidify this latter solution with acetic acid and ex- but much less potent action.-R. G. MACFARLANE. (W. H. H.) tract with ether, wash the ether solution until neu- Lancet, 250, 888(1946). Sulfonamide-Concentration of, in Bronchial or tral, filter, and evaporate. The residue is virtually pure protoporphyrine. White rats injccted sub- Respiratory Tract Fluid Following Oral Administracutaneously with protoporphyrine excrete increased tion. Sulfanilamide, sulfathiazole, sulfadiazine, and sulfamerazine were given b y stomach tube in a dose amounts in the feces. No urinary protoporphyrine nor increase of urinary coproporphyrine excretion of 0.1 Gm./Kg. body weight t o some 200 animals followed the injection. Much of the injected mate- (including guinea pigs, rabbits, cats, dogs, and rial remained at the site of injection. There is no hens). Hourly after administration the concentraevidence that the rat is able t o convert protopw- tion of the respective sulfonamide was determined in respiratory tract fluid (RTF) and in the blood. It phyrin into coproporphyrin. Photosensitization experiments of injected white rats t o carbon-arc was found that the concentration of free and of comand sunlight were unsuccessful-I. ZELIGMAN. bined sulfonamide in RTF was practically equal to that in blood, over a period of 4 hr. from the time Proc. SOG. Exptl. Biol. Med., 61,350(1946). of administrating, indicating that these sulfonamides (A. E. M.) Riboflavin in Blood-Microbiologicai D e t e G a - freely appear in R T F after administration by mouth. Most of the sulfonamides had an expectorant effect tion of. Certain modifications of the method of in the sense that they augmented the output of Strong, Feeney, Moore, and Parsons are suggested. RTF.-ELDoN M. BOYDand J. A. S. DORRANCE. An acid extraction is favored since the extract is Reu. can. biol., 5, 257-64(1946). (A. P.-C.) more stable and therefore facilitates routine analyThiamine-Urinary Excretion of, as a Charactersis. T o 1 cc. of blood is added 4 cc. of hydrochloric acid, the mixture is autoclaved at 15 Ib./sq. in. istic of the Individual. The thiamine excretion of for 15 min. and placed in a dark place t o cool; the young men on a constant diet shows 32- to %fold mixture is stable for 24 hr. When required it is variations for each group with an intake of 1 and 2 neutralized with sodium hydroxide. brought t o b H mg., respectively, a
26

PHARMACEUTICAL ABSTRACTS

serum and 0.6 cc. of 1.25% resorcinol in redistilled water is always less than 30 in healthy individuals. Higher values should always lead to the suspicion of a n active lesion. By constructing a curve it is possible t o follow the evolution of the disease and t o Soc. Exptl. Biol. Med., 61, 348(1946). (A. E. M.) decide whether a n operation is indicated. The ease Thymol Turbidity Test-Persistence of Elevated with which the test can be made should allow of extensive practical app~ications.-BRocQ-RoussEu. Values for the, Following Infectious Hepatitis. Values for the serum thymol turbidity test show a Through Chimie 6.’industrie, 53,393( 1945). (A. P.-C.) delayed rise and fall following a n acute attack of infectious hepatitis. Recurrences of the disease proVitamin K and Globular Agglutination. Accordduced a marked increase in the thymol reactivity ing to Stoppelman a transfusion may prove difficult, of the serum which persisted long after the symptoms or even impossible, in a subject who was adminishad disappeared. The thymol reaction may show a tered synthetic vitamin K within the preceding 24 delayed and prolonged response to liver injury.hr. In order t o check these findings synthetic HENRYG. KUNKELand CHARLESL. HOAGLAND.vitamin K was administered orally or intramuscuPIOG.SOC.Exptl. Biol. Med.. 62,258(1946). larly to a number of individuals. Ten tests were (A. E. M.) made of which 5 were with Davitamon. 3 with Transamination Enzyme of the Rat Kidney. The Synkavit, and 2 with Karane, using doses which results obtained do not indicate the existence of a were considered by Stoppelman t o be liable to prophysiological role for the transamination mechanism duce aberrant agglutinations. NO change in the in the rat kidnCy. The decrease of the enzyme ac- agglutinating power of the serum for erythrocytes tion with age is of a magnitude such a s would be ex- could be noted after administration of these synpected with the increase in the mass of renal tissue thetic vitamin K preparations. With corpuscles consistent with growth, whereby is provided a rela- 8 to 11days old there were 2 exceptions to the general tively constant over-all activity for the kidneys rule, which can be explained by Thomsen’s phenomeof the rats of both sexes throughout their existence. non and were not obtained with fresh corpuscles. Parathyroid, adrenal, and thyroid hormone prepa- Patients treated with vitamin K would therefore rations did not appear to influence the enzyme ac- not seem t o be exposed to transfusion accidents by tivity significantly, which might suggest that abnormal agglutination of the donor’s erythrocytes. DEWEERDT. Le Sang, 16, 218-23(1944); changes in metabolism are not reflected in variations -W. in the transamination process. A deficiency of through Chimie 6 industrh. 53, 406(1945). (A. P.-C.) arginine in the diet is not responsible for any definite alteration in the activity of the enzyme.-H. L. Vitamin K Substitutes-Prothrombin Level and W n L w s and E. M. WATSON. Rev. can. biol., 5 , Effect of, in Thrombocytopenic Purpura in Rats. (A. P.-C.) 265-69( 1946) (in English). The prothrombin level is not reduced after antiVernes’ Reaction (Flocculation of Resorcinol). platelet serum to rats nor are the manifestations of Tuberculous serums flocculate in presence of exmrimental thrombocvtoDenic D m u r a modified phenols, and more particularly resorcinol, at lower by- vitamin K substitut&.LMARiORk B. ZUCKER. dilutions than normal serums. The plotometric Proc. SOC.Exptl. Biol. Med., 62, 245(1946). number of a mixture of 0.6 cc. of perfectly clear (A. E. M.) the Rat. Both substances afford a degree of protection against hepatic cell necrosis due t o dietary deficiencv in the rat. The comDounds are not l i ~ o tropic.-joHN GREENand A. BRUNSCHWIG.Pioc.

PHARMACOGNOSY VEGETABLE DRUGS Aconites of Indian Market. Eight species of aconite occur on the Indian market and can be divided into 5 groups, viz.: (1) European, derived from Aconitum napellus; (2) Indian napellus, derived from A . chasmanthiaim, often adulterated with A . heterophyllum or A . palmatum; (3) Ferox variety, consisting of roots from A . deinorrhizum and A . balfourii, occasionally mixed with A . spiEatum and A . lacinkturn, (4) White aconite, a mixture of A . deinorrhizum and A . balfourii; and (5) Atis root, a nonpoisonous root from A . heterophyllum. The macroscopical and microscopical characters of the whole roots derived from these species are described and illustrated. A table giving the chemical reactions of a n alcoholic extract of each root with several common chemical reagents is included. The results are summarized in a scheme by means of which seven of the varieties can be distinguished from each other.-S. C. DATTA,B. GUPTA,and I. N. BAL. Indian J. Pharm., 1, 6(1945); through Quar6, J. Pharm. Phurmacol., 19, 205(1946). (S. W. G.) Galls-Coloring Matter of. The coloring matters of 6 specimens of galls produced by fungi have been isolated and examined. They proved to be pigments previously described by Nierenstein and Swanston. The galls produced by Albugo candida Pers. on the leaves of Capsella bursa pastoris L., by Exobasidium rhododendri Cram. on the leaves of Rhododendron hirsutum L. and R. ferrugineum L., all yielded riestellin. Melampsorin, xestophanesin and pontanin were obtained from the galls produced

by Exoascus amentorum H. Schneider on the fruits of Alnus incana Web., by Puccinia adoxce Haberl. on leaves, twigs and buds of Adma moschattellinu L., and Ustilaxo maydis Guttenberg on tRe leaves of Zeu mays L. In all cases the yields were small. the maximum being 0.27yo.-M. NIERENSTEIN and C. H. WALTON. Biochem. I.,29,481(1945). (S. W. G . ) Gum Acacia-Causes of the Solubility of. The heartwood, sapwood, and bark of 3 different species of Acacias were treated with Asterula gummipara and 3 species of native (French) fungi. A . gummipara gave rise t o the formation of water-soluble gum, whereas the other fungi produced gums that were practically insoluble. It is concluded that the solubility of gum acacia, as contrasted with the insolubility of native French gums, is attributable not to the species of trees on which it is produced, but to the nature of the organisms whose action produces it. -L. LUTZ. Ann. pharm. franc., 3, 58-59(1945). (A. P.-C.) Myrobalanitannin-Distribution of. Myrobalanitannin, which was isolated from myrobalans, the fruit of Terminalia chebula Retz.. has been shown t o be present in a large number of roots, rhizomes, barks, leaves, fruits, galls, etc., a list of which is gtven. That this tannin is luteoic acid 5-biglucoside and not a diglucoside, luteoic acid 4:5diglucoside, has been confirmed by the hydrolysis of the product of methylation of the tannin, which gave tetramethylellagic acid-M. NIERENSTEIN and J. POTTER. Biochem. J., 39, 390( 1945). (S. W. G.)

PHARMACOLOGY, TOXICOLOGY AND THERAPEUTICS Palisade Ratio Value of Atropa Belladonna and A. Acuminata. The palisade ratio frequency of Atropa belladonna has been shown t o conform to a normal distribution with a mean of 6.0 and a standard deviation of 1.47. The limiting values of such a distribution (3u values) are 1.6 and 10.4, while the mean of 20 readings from a powder derived from many leaves may be expected t o fall within the range 5.0 t o 7.0. The palisade ratio frequency of commercial Indian belladonna leaf (imported At ropa acuminata) has been shown t o conform to a n asymmetric distribution with a mean of 8.2, a mode of 7.8, and limits of 4.0 and 13.5. The mean of any 20 readings from a powder derived from many leaves may be expected t o fall within the limits 6.9 and 9.2. The palisade ratio frequency of Atrope acuminata (English-grown samples) has been shown t o conform to a normal distribution with a mean of 4.7, and a standard deviation of 0.84. The limiting values of such a distribution (3 u values) are 2.2 and 7.2, while the mean of 20 readings from a powder derived from many leaves may be expected to fall within the range 4.1 t o 5.3. The palisade ratio frequency of Phytolacca leaf found as a n adulterant in the commercial Indian belladonna leaf conformed to a normal distribution with a mean of 3.5, and a standard deviation of 0.66 (3 u limits 1.5 and 5.5). Palisade ratios as determined are as follows: Atropa belladonna, 1.6 t o 6.0 t o 10; Atrope acuminata (commercial Indian leaf), 4.0 to 13.5, with mode 7.8 and mean 8.2; Atropa acuminata (Englishgrown leaf), 2.2 t o 4.7 t o 7.2; Phytolacca species, 1.5 t o 3.5 t o 5.5. Some evidence is given indicating that the existence of the 2 palisade ratio ranges recorded here for Atrope acuminata may be an effect of GEORGE. Quart. J. Phurm. hybridization.-E. (S. W. G.) Pharmacol., 19, 144-54( 1946). Plants-Stabilization of, by Drying. The process proposed consists in heating the fresh plants by induction (e.g., passing between the plates of a condenser connected t o an oscillator, or directly inside the coil of a n oscillating circuit). Tests carried out on the leaves of Aucuba japonica and on mustard flour showed that the enzymes were quickly inactivated or destroyed without appreciable modification in the appearance of the treated product. It is suggested that the process would be economically applicable t o the drying of plant products in spite

27

of the high cost of the electric calorie because it is necessary to heat only the material itself (and not a whole autdave).-ALFRED DANIEL-BRUNET and MICHELLAURENT. Ann. pharm. franc., 3 , 33-36 (1945). (A. P.-C.) flcance of, as Differential StomataI Index-S Character. III. S t u r s in the Genera Atropa, Datura, Digitalis, Phytolacca, and in Polyploid Leaves. Further evidence has been provided of the constancy of the stomatal index of a plant species. The stornatal indices of Datura Stramonium, D. tatula, D . metal, D. inermis. Digitalis purpurea, D. Tanata, D. luteu. D. Thapsi, Phytolacca america@a, P . acinosa, and of authenticated material of Atropa acuminata have been recorded. Stomatal indices suggest that Datura inermis should be classified as a variety of D . Stramonium, but that D . tutula should be retained as a distinct species. The stomatal index in polyploid plants is lower than in the corresponding diploid controls. The stornatal index does not vary significantly at different positions upon the leaf surface; it is independent of leaf size or of plant habitat, and it is t h e same for different varieties within a species. The value has been found to be more uniform upon the lower surface of a leaf than upon the upper surface, except for isobilateral leaves, Stomatal indices of 16 species from 6 genera have been determined. Co-generic species may be differentiated by means of this index. The range and average of sample values (based upon 5 leaves per sample) are tabulated. Stomatal indices may be determined upon the entire, crushed, or powdered leaf and when the powdered drug is present in galenical preparations.-J. M. ROWSON Quart. J. Phurm. Phurmacol.. 19,136-43( 1946). (S. W. G . ) Wood Charcoals-Further Obsemations on. The microscopic characters of the fragmentary charred vessel walls (identification particles) of the following woods: apple, box, broom, hawthorn, hornbeam, plane and walnut are presented as a key for the identification of these hardwood charcoal powders. These observations plus those in a n earlier paper [ J. Chem. SOC.Ind., 62, 141(1943)1 cover all of the commoner English dicotyledonous types.-L. G. G. WARNE. J . Chem. SOC.Ind., 63, 124(1944). (W. T. S.)

PHARMACOLOGY, TOXICOLOGY, AND THERAPEUTICS PHARMACOLOGY Adrenalectomy and Gastric Secretion. Adrenalectomized rats in good general condition show marked diminution of gastric secretion following stimulation with Doryl. Gastric juice of such rats contains little or no free acid, only small amounts of total acid, is low in enzyme content, and rich in mucin. Medullectomy alone does not depress gastric secretion. Artificial shock does not disturb gastric secretion. Increased intake of sodium chloride and treatment with desoxycorticosterone acetate do not restore the gastric secretory function of adrenalectomized rats. Following administration of adrenal cortex extract (Upjohn), normal gastric secretion is restored. It is concluded that different secretory functions (gastric secretion, lactation, renal-tubular secretion) depend on the adrenal hormone which governs carbohydrate metabolism.E. TUERKISCHER and E. WERTHEIMER.J. Endocrinol., 1, 143-51(1945). (A. P.-C.) Adrenalin-Gas-Gangrene Following Injection of. .A case of gas-gangrene developing at the site of injection of adrenaline is described. Experiments in guinea pigs showed that the intramuscular injection of adrenalin greatly reduced the lethal dose of

washed Cl. welchii injected with it. The local injection of adrenalin may determine the production pf a focus of gas-gangrene in animals given washed C1. welchii by the intravenous route. I n gas-gangrene following injections of adrenalin in man the source of infection is more likelv t o be exoeenous than endogenous.-E. V. COOPER. Lancet 250, 459( 1946). (W. H. H.) Amino Alcohols, Aromatic, of the Type ArC H O H C H n N R t T h e Inhibition of Choliiesterase by. The cholinesterase of human plasma is effectively inhibited by phenanthrene amino alcohols. The inhibition is related to the size of the dialkylamino group passing through a maximum with the dipropylamino group. Certain changes in the phenanthrene nucleus tend t o diminish this action. Much higher concentrations are required to inhibit the cholinesterase of the erythrocytes, a fact which may be utilized to differentiate the enzymes. Although-these compounds are antimalarials, there is no relation between the 2 actions.-C. I. WRIGHT. (M. W. G.) J. Pharmacol., 87, 109-2q1946). Androgens'-Gonad Stimulation by, in Hypophysectomized Pigeons. Spermatogenesis may be restored in the atrophic testes of hypophysectomized

28

PHARMACEUTICAL ABSTRACTS

pigeons by androgen treatnieiit, and the same treat- succinate and acid oxalate of j3-dimethylaminoethyl ment may produce follicular growth in the atrophic benzhydryl ether (Benadryl) have an histaminolytic ovaries of hypophysectomized female pigeons. action of the same order of magnitude as the hydroLarge doses of androgen given to adult pigeons dur- chloride. The acid succinate is less toxic than the ing the nonbreeding season or to immature male hydrochloride on a molar basis suggesting an anionic pigeons did not stimulate the testes but did stimu- influence. Quaternary ammonium derivatives of late the ovarian follicles of immature female pigeons. the base, while entering the class of choline derivatives, retain potent histaminolytic properties and The role of androgens in maintaining testicular function and in relation to uituitarv functions are a t the same time exhibit considerably more potent discussed.-J. P. CHU and S . S. You. J. Endo- atropine-likc action than salts of the tertiary type. CLAUDEV. WINDER,et al. J. Phurmucol., 87, 121crinol., 1, 431-35(1946) (A. P.-C.) (M. W. G . ) Anterior Pituitary Extract--"Growth" in Relation 31(1946). to the Diabetogenic and Pancreotropic Actions of. Blood-Coagulating Product. The purpose of the Fifteen English rabbits maintainiug a n almost invention is to prepare thromboplastin and proconstant body weight and urinary volume on a prac- thrombin free from antithrombin and soluble in tically fixed caloric intake were intensively treated saline. Repeated salt precipitations up to 5 times, with crude ox anterior pituitary extract. The ani- of a tissue extract a t a pH of 9 removes antithronibin. mals as a result of this treatment increased actually If prothrombin is adsorbed on magnesium hydroxide or relatively in weight on a definitely reduced caloric in presence of a large quantity of antithrombin the intake; the diminution i n food value was due mainly latter is absorbed also; if, however, most of the antit o loss of appetite, but also partly to dissipation thrombin is removed previously, the adsorption on of energy through temporary glycosuria and keto- magnesium hydroxide permits a complete separanuria. The fact that the injected rabbits relative tion. Calcium salts must be excluded. Example t o their caloric intake excreted an excessive urinary I: Lung tissue is extracted with a n equal quantity volume leads to the inference that fluid retention of saline a t 5'. Prothrombin is adsorbed on magplayed no part in their actual or relative increase in nesium hydroxide. The separated solution is prebody weight. The pancreatic islets of the treated cipitated with a n equal volume of ammonium sulanimals, while numerically normal, were on the aver- fate solution saturated at 5" and the precipitated age more than twice as heavy as those of a control thromboplastin is dissolved in saline. The purisenes. The actual or ,relative increase in body fication by precipitation is repeated and finally the weight of the injected rabbits on a reduced food ammonium salt is removed by dialysis. By evapvalue indicates that anterior pituitary extract re- oration in vacua dry, soluble thromboplastin is duces the metabolic rate and probably also increases obtained. Example 11: Oxalated ox plasma is anabolism. These effects are attributed to the diluted with water and adjusted with acetic acid to diabetogenic action of the extract on the one hand, a PH of 5.3. The precipitate formed during 2 hr. and on the other t o increascd pancreatic islet func- is separated and suspended in a solution of 0.0S5'j{1 tion induced through the pancreotropic property of potassium oxalate and 0.860/, sodium chloride. A the preparation. The. above observations support solution of prothrombin and antithrombin results. the suggestion of Young [Brit. Med. J., II, 897 To each 6 L. of this liquid is added 10 to 15 cc. of (1941)l that the prediabetic excess of height and 8% to 10% suspension of magnesium hydroxide. weight in children and adults, respectively, is due This removes fibrin and other impurities. Theret o an elevated hypophysial-pancreatic balance, fail- after 1 L. of the magnesium hydroxide suspension is ure of which through islet exhaustion results in added for each 750 units of prothrombin. The diabetes ElefitUS.-ROBERTSON F. OGILVIE. J . magnesiun mixture is decomposed with carbon di(A. P.-C.) Endocrinol. 4, 152-5% 1945). oxide under pressure. The solution is dialyzed Antimonials-The Tissue Distribution and Ex- until acetic acid produces a precipitate a t 5.3. The cretion of Four Organic, After Single or Repeated cleared solution is then precipitated with acetic acid. Administration to Normal Hamsters. Following a The prothrombin thus obtained is of high potency. single injection of 4 therapeutically active anti- Thrombin is prepared from thromboplastin, promonials (tartar emetic, anthiomaline, stibanose, and thrombin, and calcium salt, precipitated with aceneostibosan) the Sb was always localized in the liver. tone and redissolved in water. Dialysis affords With the quinquevalent compounds, a high concen- additional purification.-HARRY P. SMITH,assignor DAVIS& Co. U. S. pat. 2,398,077, April tration of Sb was found in the spleen. Fifty per t o PARKE, (A. P.-C.) cent of the trivalent compounds were excreted in the 9, 1946. intestine (probably Via the bile) while the quinqueDesoxycorticosterone Acetate-Concentration of valent compounds are excreted oia the kidneys. Chloride, Sodium, and Potassium in Blood of Guinea Chronic toxicities were also studied.-ALFRED GELL- Pigs Treated with. Castrated female guinea pigs were treated with fibromatogenic doses of diethylHORN,et al. J . Phurmacol., 87, 169-80(1946). (M. W. G.) stilbestrol. A second group was treated with diAntimony-An Evaluation of the Rhodamine B ethylstilbestrol and quantities of desoxycorticosterone acetate sufficient to prevent estrogen inMethod for the Determination of. A technique for determining antimony with rhodamine B is de- duced abdominal fibroids. The average fibrous scribed within a range of 2.0 t o 15.0 y of Sb. It can tumoral effect diminished considerably. The concentration of chloride, sodium and potassium in the be determined in the presence of tissue without M. E. KRAHL,and blood of both groups was within normal limits. dk?iculty.-ALFmD GBLLHORN, This proves that the antifibromatogenic quantity of J. W. FBRTIG.J . Pharmacol., 87, 159138(1946). desoxycorticosterone acetate is smaller than the (M. W. G.) Barbiturates-The Response of the Isolated Frog doses which interfere with the ionic balance.Heart to Different. The isolated frog heart was de- EMILIO ALVAREZand FLORENCIOFUENZALIDA. pressed by all 10 barbiturates studied. There is Proc. SOC.Exptl. Biol. M e d . , 62, 132(1946). (A. E. M.) considerable variation in the concentration of drug required for activity and the barbiturates may be Diethylstilbestrol-Induction of Lactation in M. Heifers by a Single Injection of Esters of. Lactagrouped according t o this activity.-CHmEs GRWERand GOLDIEF. KBYSER. J. Pharmacol., 87, tion can be induced in small virgin heifers by a single 104-8(1946). (M. W. G.) injection of diethylstilbestrol in ester form. The BenadryI-Myotropic, Spasmolytic, Histamino- simultaneous injection of a slowly acting and a lytic, and Atropine-Like Actions of. The acid rapidly acting ester seems t o be the most effective

PHARMACOLOGY, TOXICOLOGY AND THERAPEUTICS method. The best yield, a daily average at the peak period of 13 Ib., was obtained from a heifer injected with 0.25 Gm. of dilaurate and 0.25 Gm. of dipropionate. Allowing for the small size of the heifers, this combination of esters, given as a single injection, seems t o induce lactation as effectively as does the implantation of tablets of diethylstilbestrol or and R. E. GLOVER. J. hexestro1.-A. S. PARKES (A. P.-C.) Endocrinol. 4, 9O-102( 1944). Estrogen Excretion in Milk from Estrogenized Cattle. Small amounts of hexestrol (1 t o 2 y per 20 fl. 02.) added to normal milk can be extracted with 60% t o 100% recovery. The amounts of estrogen present in milk from heifers treated with s y n thetic estrogens is too small for assay by direct feeding t o rats. Samples of experimental milk were extracted b y the continuous ether extraction method and roughly assayed by subcutaneous injection or intravaginal application in ovariectomized rats. The milk from heifers implanted with hexestrol contained 0.01 to 0.5 y estrogen per 20 fl. 02.; from diethylstilbestrol-implanted heifers, 0.4 t o 1.O y . Single determination on the blood and urine of a heifer receiving 20 to 24 mg. of dienestrol daily by mouth gave dienestrol concentrations of 5 y per L. of blood and 2 mg. per L. of urine.-W. LAWSON, S. W. STROUD, and P. C. W n L I m s . J. Endocrinol., 4, 83-89( 1944). (A. P.-C.) Estrogen Tablets, Synthetic-Artificial Induction of Lactation in the Bovine by Subcutaneous Implantation of. Lactation was induced in nulliparous heifers and dry cows b y the subcutaneous implantation of large numbers of small tablets of diethylstilbestrol or hexestrol. Individual variations in response were large, but in some cases the lactation curve was comparable with that of normal lactation. The best response was obtained with a dry cow which gave a maximum yield of 30*/4 Ib. daily and a total yield of 7400 lb. Implants totalling 5.0 and 2.5 Gm. were equally effective, and there appeared t o be no difference in efEcacy between diethylstilbestrol and hexestrol. Copious lactation was also induced in nulliparous heifers and dry cows by the subcutaneous implantation of 1 or 2 tablets of hexestrol weighing approximately 1000 mg. . Tablets of diethylstilbestrol implanted into bovines were absorbed faster than tablets of hexestrol. The principal drawbacks associated with the use of implants consisting of large batches of small tablets were tablet fragmentation and migration; neither happened when large hexestrol tablets were used. The estrogen treatment was, in most cases, accompanied by a nymphomaniae syndrome, which, in 20% of the experiments in which small tablets were implanted, culminated in and F. H. MALPRESS. pelvic fracture.-S. J. FOLLEY J. Endocrinol., 4, 1-18( 1944). (A. P.-C.) Estrogen Treatment of Cattle: Induced Lactation and Other Effects. Estrogen treatment was given to 140 cows and heifers, nearly all with tablet implants of stilbestrol or hcxestrol; nhservations were itiadr on rhangrs in lhe ovaries, reproductive tract, udder, and behavior. During treatment follicle growth ceased and occasionally the corpus luteum persisted; after removal of the implant follicle growth began, and ovulating was resumed, sometimes after a transient period of follicular cysts; an increased frequency of double ovulations was notea. After the corpus luteum died out there were irregular heats; the frequency and intensity of these varied greatly, in a few animals behavior seemed characteristically male. Relaxation of pelvic ligaments together with repeated jumping sometimes led t o fractures of the pelvis. The heifers used were animals which had failed to get in calf (in some it was anatomically impossible); after treatment a number of those with normal organs

29

were observed and a large proportion got in calf. Mammary growth in heifers occurred. Drying off of lactation, and its initiation in cows and heifers, followed implants. In the presence of a persistent corpus luteum development of secretion was suppressed: Lactation did not result in every case, and Sometimes the volume of secretion was low, but many animals gave commercial yields (records are not complete, but over 130 tons of milk were produced). Data are given on rates of tablet absorption; very rapid absorption within the peritoneal cavity was observed. There is some discussion on the possible mechanisms involved, particularly in connection with lactation.- J. HAMMOND, JR., and F. T. DAY. J. Endocrinol. 4, 52-82 (1944). (A. P.-C.) Estrogens-Enterohepatic Circulation of. The duration of estrus in rats injected with estrone or stilbestrol was determined daily b y vaginal lavage. The estrogenic effect of stilbestrol was as usual more prolonged than that obtained with a similar amount of estrone. When the enterohepatic circulation of estrogens was eliminated b y severing the bile duct, the estrogenic effects of estrone and stilbestrol were definitely prolonged. Since the effect of cutting the bile duct was t o prolong estrus it seems evident that the enterohepatic circulation of stilbestrol does not account for the known long-lasting effect of this estrogen. After the bile duct was severed both estrone and stilbestrol were especially prolonged in action following subcutaneous injections. This is thought t o imply delayed absorption, rather than delayed destruction of these estrogens b y the liverFREDERICK E. EMERY and HERBERTE. JOYCE. J . Endocrinol, 4, 371-74( 1946). (A. P.-C.) Estrogens-Ovarian Stimulation by. 11. Stimulation in the Absence of Hypophysis, Uterus, and Adrenal Glands. The ovarian stimulation produced b y stilbestrol injections in immature hypophysectomized rats is unaffected b y removal of the uterus, or of the uterus and adrenal glands. There is no evidence that this effect of estrogens is a n indirect one.-P. C. WnLuras. J. Endocrinol. 4, 125-26( 1945). (A. P.-C.) Estrogens, Synthetic, and Anterior-Pituitary Extracts-Induction of Lactation in Goats and Cows with. Simultaneous treatment with cstrogen and ox anterior-pituitary extract induced lactation in virgin goats sooner than treatment with cstrogen alone. In 2 out of 5 experiments on cows or goats in which prolonged estrogen treatment failed t o induce lactation, the institution of anterior-pituitary injections was followed by copious milk secretion.. Anterior-pituitary extract exerted a galactopoietic effect at the peak of lactation induced b y estrogen treatment in maiden heifers or virgin g o a t s . 4 . J. FOLLEY, F. H. MALPRESS,and F. G. YOUNG. J. Endocrinol., 4, 181-93(1945). (A. P.-C.) Estrogens, Synthetic-Artificial Induction of Lactation in Bovines by Oral Administration of. A preliminary experiment in which 8 heifers were given daily doses of hcxcstrol or dit-nestrnl in their food or drinking water indicated that lactation could be satisfactorily induced in this way. A further experiment involving 32 heifers, in which diethylstilbestrol or dienestrol was fed daily, gave less encouraging results, only 19 of the animals being brought into lactation, and the general plane of response being markedly lower. Variability of the response in all its quantitative aspects was a feature of these experiments. The yields generally were inferior to those given in the implantation experiments (preceding abstract), and far more estrogen was needed t o evoke responses. The general “condition” (in the sense in which the word is used in animal husbandry) of the animals suffered in no way from the treatment, and nymphomaniae effects

30

PHARMACEUTICAL ABSTRACTS

were not pronounced. No pelvic fractures were caused, but 2 serious cases of vaginal and rectal prolapse were encountered. Thirty of the animals used in the main experiment were subsequently served, and 25 became pregnant, in many cases t o the b s t service. I t is estimated that in the bovine, the oral administration of synthetic estrogens results in the utilization of less than 10% of the dose given. The special problems presented by rumen activity and incomplete absorption from the alimentary canal are considered. The extent to which the factor of age may influence the response is also disand F. H. MALPRESS. J. cussed.-S. J. FOLLEY (A. P.-C.) Endocrinol., 4, 23-36( 1944). Estrogens, Synthetic-Chemical Composition of Bovine Mammary Secretions Induced by the Subcutaneous Implantation or Oral Administration of. The mammary secretions produced by heifers artificially brought into lactation by treatment with synthetic estrogens were a t the outset colostral in nature, but the composition gradually changed t o that characteristic of milk of good chemical quality at a rate roughly proportional to the rate of increase in yield. I n general, a daily yield of 5 Ib., sometimes much less, could be regarded as a guarantee of normal composition.-S. J. FOLLEY and F. H. MALPRESS. J . Endocrinol.. 4, 37-42( 1944 (A. P.-C.) Fertilization of Eggs in Hypophysectomized Rats. Ovulation was produced in hypophysectomized female rats by injections of serum and chorionic gonadotropins. These rats were mated with normal males and their eggs collected 2 days later and compared with eggs .from normal mated females. The average number of eggs recovered from the Fallopian tubes of the experimental rats was 10.4; that from the normal rats was 4.9. I n the experimental rats 60% of the eggs were normal fertilized 2cell, 3-cell, or 4-cell eggs; 9% were 1-cell eggs of uncertain normality, and 31% were degenerate. There were only 5% of degenerate eggs in the normal rats. The proportion of degenerate eggs is not related to the number of eees shed Der ovarv.-I. W. ROWLANDS and P. C. W~LLIAMS:J . EGdocrinol., 4, 417-21(1946). (A, P.-C.) Filariasis in the Cotton Rat-Chemotherapy of, by the Administration of Stibanose (Solustibosan). The repeated administration of stibanose t o the cotton rat eradicated the fikria.-JAMES T . CULBERTSON and ELIZABETH PEARCE.J. Phurmacol., 87, 181-83(1946). (M. W. G.) Fluoroacetate- Studies on the Pharmacology of I. Species Response to Fluoroacetate. Fluoroacetate as the methyl ester injected into 11 s p e c k of mammals and the chicken and frog showed no similarity to other halogen derivatives of acetic acid. Death in rabbits, goats, horses, and spider monkeys is due primarily t o ventricular fibrillation. The dog and guinea pig exhibit central nervous disorders, especially epileptiform convulsions and death is due to respiratory failure. The rat and hamster exhibit bradycardia without ventricular fibrillation. The LDwS for most species are given and range from 0.06 to 14.0 mg./Kg.-MAVNARD B. CHENOWETH and ALFREDGILMAN. J. Pharmacol., 87, 90 (1946). (M. W. G.) Folic Acid Requirements of Chicks for Growth, Feathering, and Hemoglobin Formation. Requirements found were a s follows: For survival to 6 wk. of age, 25 y/lOO Gm.; for growth and hemoglobin formation at 4 wk. of age, 45 y ; for growth a t 5 wk., 45 y . but for hemoglobin formation a t 6 wk., 35 y ; for feathering at 6 wk. not le4s than 55 y/100 Gm. of diet. The additioii of 10/(1or 2v0 succinylsulfathiazole to the diet did not exert any influcncc on growth, feathering or hemoglobin formation.-

.

E. I. ROBERTSON, el al. Proc. Soc. Exptl. Biol. Med., (A. E. M . ) 62, 97( 1946). HexestroI-Use of Tablets Containing 50%. .for the Artificial Induction of Lactation in the Bovine. Experiments were carried out on the use of subcutaneous implants of tablets containing 50% hexestrol, 49% lactose, and 1% stearic acid for artificial induction of lactation in maiden heifers and dry cows; individual variations in response were large, but satisfactory responses were given by 2 heifers and 1 dry cow to low total doses of estrogen. The responses of 6 heifers giving small amounts of secretion to further implants consisting of pure hexestrol tablets were also variable; in 2 cases marked increases in yield resulted. Symptoms of nymphomania were observed in all animals, but none suffered pelvic fracture. Of 6 animals retained for breeding after cessation of treatment, 5 became pregnant to the first mating; all delivered male calves, 2 being born dead and another prematurely. In the case of implants consisting of 50-mg. tablets containing 50% hexestrol, there was a tendency for some of the tablets to become broken in sifu, though not to any greater extent than small tablets of pure hexestrol. Under the conditions of the experiments tablets containing 50% hexestrol were absorbed more slowly than pure hexestrol tablets of comparable size.-S. J. FOLLEY, D. L. STEWART, and F. G. YOUNG. J . Endocrinol. 4,43-52(1944). (A. P.-C.) Hormone Action-Experimental Control by, of the Estrus Cycle in the Ferret. Tablets of estrogen (either estradiol or a diethylstilbestrol ester) implanted into anestrous or oophorectomized ferrets will produce and maintain estrus for an indefinite period. Progesterone tablets implanted into ferrets with experimentally induced estrus will inhibit such estrus and on their removal estrus will be resumed. Thus, progesterone antagonizes estrogen. There is some evidence that intact anestrous ferrets may be brought on heat by less implanted estrogen than that which is required to induce heat in oophorectomized fcrrcts. There is some evidence that testosterone may antagonize estrogen in the same way as progesterone does. The capacity for response to introduced estrogen may vary in different ferrets and a t different times in the same ferret. Two 15-tng. stilbestrol dipalmitate tablets were found regularly to be sufficient t o cause swelling of the vulva; the mean daily absorption per tablet was 4.4 y , equivalent to 1.6 y of free stilbestro1.F. H. A. MARSHALL and J. HAMMOND, JR. J. En(A. P.-C.) docrinol. 4, 159-68(1945). Hormone Tablets-Some Factors Mecting the Absorption Rate of Subcutaneously Implanted. The influence of various factors on the absorption of tablets of hexestrol and testosterone in rats was studied. Over a pressure range of 12.4 t o 62.0 tons per sq. in. the absorption rate of compressed hexestrol tablets was for all practical purposes independdent of the pressure used in making them. The initial absorption rates per unit area of cast and compressed tablets of testosterone were approximately equal. The absorption rate of cast cylinders of testosterone obeys a mathematical law deduccd on thc assumption that absorption rate a t any instant is proportional to the surfacc area a t that instant. The value found for the initial absorption rate of cast tablets of testosterone in rats was approximately twice the value found previously in men. Tablets of hexestrol or testosterone containing 25, 49, or 50% lactose (diluted tablets) were absorbed a t approximately the same rate as, certainly n o faster than, tablets of pure hormone. During the latter stages-of absorption, the absorption rate of diluted tablets of testosterone was much less than that of tablets of pure hormone. The

PHARMACOLOGY, TOXICQLOGY AND THERAPEUTICS probable effects of ghost formation on the absorption of compressed tablets are discussed in the light of the above findings.-A. T. COWIE and S. J. FOLLEY. J . Endocrinol., 4,37&85( 1946). (A. P.-C.) Iodinated Proteins-Preparation and Biological Effects of. I. Introduction.-J. RARCROFT. J. Endocrinol., 4,219-20( 1945). II. h e aration and Properties of Physiologically Active Iolinated Proteins. The preparation is described of iodinated ox plasma, iodinated Ardein (the mixed protein from ground nut prepared by I. C. I. (Explosives) Ltd., Ardeer), and iodinated casein. The total iodine and acid-insoluble iodine contents of all preparations were determined ; the acid-insoluble iodine value was used as a guide in deciding whether any preparation should be used for biological experiments. Iodinated plasma preparations contained up to 1.5% acid-insoluble iodine, iodinated Arbeifi preparations contained u p t o 1.5% acid-insoluble iodine, iodinated Ardein preparations contained u p t o 1.4%, and iodinated casein preparations up to 2.8%. Iodinated products of all 3 proteins have been shown elsewhere t o be active in increasing the milk secretion of cows and in accelerating tadpole metamorphosis. Of the 3 types of iodinated protein obtained, iodinated casein was the most satisfactory to prepare on a large scale; better yields of product were obtained, and these showed the greatest biological activity. No advantageous departure from the conditions given by Ludwig & von Mutzenbecher [ Hoppe-Seyl. Z.,258, 195(1939)] for the preparation of biologically active iodinated proteins was found; the process of high temperature incubation of the iodinated product which was found by Reinecke, Williamson, and Turner [ J.‘Biol. Chcm., 143, 285( 1942)l to give highly active products was used in the later preparations of iodinated casein.ROSALIND PITTRIVERSand S. S. RANDALL.Ibid., 221-36. 111. Effect of Iodinated Protein Feeding on the Lactating Cow. Experiments in which iodinated proteins were fed t o milking cows are described. Early experiments with iodinated proteins of low thyroidal activity resulted in little effect on milk production or metabolism, and iodism symptoms rapidly occurred in the experimental animals a t the high doses used. A highly active preparation, iodinated Ardein N4MB, stimulated milk production very considerably. and all available evidence showed a concomitant increase in the metabolism of the individual cows. Even following a Iong period of treatment the evidence collected did not indicate that any permanent damage had been done t o the cow.-K. L. BAXTER. Ibid., 237-65. IV. Effects of Iodinated Casein. Experiments were carried out using preparations of iodinated casein, designed t o elucidate the factors responsible for the variation in the response t o ioditlated protein feeding, and t o find whether iodinated proteins can be used t o increase milk production under practical conditions. Of 3 preparations of iodinated casein fed t o dairy cows, 2 were active and 1 was not; this result was in substantial agrecment with the results of assays with tadpoles. Coating iodinated protein with solid stearic acid and variation in the basal ration of the experimental cows were without any effect on the potency of the preparation; both heifers and cows, and Guernsey and Shorthorn cattle, responded to treatment with iodinated casein. The response t o a n iodinated protein is intimately related t o the stage of lactation of the cow. In early lactation the response is small, and a t the end of lactation it is not possible t o elicit a response. ’ In mid-lactation the percentage response increases as lactation declines, while the greater the initial yield the greater the response in Ib. per day. The high-yielding cow-as measured by her productivity in early lactation-responds very markedly when her yield has fallen to 2

31

gal. a day while the low-yielding cow does not. This is in reality a “lactation stage” effect, and the effect of the stage of lactation on response was confirmed by experiments with the same cow. Preliminary data suggest t h a t the same relationship applies to fat secretion, and it can be interpreted in terms of the amount of mammary tissue present and its state of functional activity. The mean percentage response in milk production is shown t o be directly proportional to dosage within a range of stimulation from 16% to 33%. The symptoms of hypermetabolism are much more severe at the higher dose levels than would be expected on the basis of a directly proportional relationship. It is suggested, therefore, that the optimal stimulation should be in the region of 20y0. Iodinated casein was incorporated in a’cattle cube which was consumed satisfactorily, and it is shown that the manufacturing process and the storage of iodinated protein cubes does not result in a reduction of the galactopoietic potency of the iodinated casein they contain. A considerable part of the loss of weight which occurs when iodinated casein is given is shown t o be prevented when the cow is given an additional supply of nutrients. A light loss of body condition was observed. The relative galactopoietic potencies of the various samples of iodinated protein which were used were expressed using iodinated casein NC3 as a standard, and the practical possibility of the iodinated protein stimulation of milk yield is b r i d y discussed.-K. L. BAXTER. Ibid., 266-99. V. Effect on Basal Metabolism of Milk from Cows Fed with Iodinated Protein. A review is given of the literature concerning the thyroxine content of milk. Over a period of 1 mo. the ingestion of 1 qt. daily of milk from cows fed iodinated protein produced no elevation of the basal metabolism, pulse rate, or blood pressure in 27 normal healthy adults. The ingestion of 1 qt. of this milk daily produced a significant inerease in weight, showing that the calorific intake greatly outweighs the effect caused by any metabolic stimulant which may be present in the milk. The literature suggests that some precautions should be taken regarding the feeding of young infants with milk obtained from cows fed iodinated protein; such a milk may contain thyroxine in excessof normal and produce toxic symptoms.-J. DOUGLAS ROBERTSON. Ibid., 300-4. VI. Further Experiments on the Restoration and Maintenance of Growth After Thyroidectomp. The retardation of growth caused by thyroidectomy in young male rats can be overcome by the implantation of. tablets of thyroxine or its mono-sodium or di-sodium salts. No detectable loss in weight of thyroxine or mono-sodium thyroxine tablets occurred in 100 days of implantation. Loss in weight of the tablets of di-sodium thyroxine over a similar period of implantation amounted t o about lo%, equal to that of thyroxine tablets implanted for 600 days. Desiccated thyroid powder or iodinated Ardein maintained and restored growth in thyroidectomized rats. The amounts of active material required t o produce minimal and maximal responses are in the ratio of 1 :200. This and other disadvantages make it impracticable to use the restoration of growth in thyroidectomized rats as a method for the biological assay of thyroidal activity.-I. W. RowLANDS. Ibid., 305-11. VII. Use of Rana temporaria Tadpoles for the Assay of Thyroidal Activity. The use of tadpoles for the assay of thyroidal activity is discussed with special reference to Ram temporaria. The restricted season for Rum tadpoles makes it difficult t o carry out a detailed examination of variables, but the following were considered: method of administration, duration of dosage, concentration and absolute amount of dose, method of assessingresults. A comparatively large number of tests were carried out, but many were preliminary in character, and mathematical treatment of the results was not

PHARMACEUTICAL ABSTRACTS

32

,

attempted. The authors' experience agrees with that of previous workers in showing that the test can give valuable indications of the thyroidal activity of a preparation, but that it is quantitatively unsatisfactory. Tadpoles should be of the same age and size and kept under the same conditions for any one test, and unknown preparations should be tested against a standard substance. It is desirable to maintain the tadpoles at a constant temperature during the test. If rearing is controlled tadpoles can be used for testing from April until July, but a further extension of the period would probably not be worth the labor entailed. The response most easily measured is the decrease in total length, ST, that tadpoles must be kept singly if the full extent of the individual variability is to be ascertained, and t o obtain statistically significant results on a large number of preparations would require more animals than could easily be kept under suitable conditions in the time available. For a short test tadpoles were kept a t 25" t o 27". dosed for 1 day, and measured at the beginning of the experiment and at the end of the 3rd J. EMMETT,and A. S. PARKES. day.-R. DEANESLY, Ibid., 312-23. VIII. Use of Xenopus Tadpoles for the Assay of Thyroidal Activity. A study of the rearing of Xenopls tadpoles under laboratory conditions was made to find out optimal conditions for obtaining large numbers of tadpoles for experimental purposes. The conclusions of previous workers concerning the induction of oviposition and mating were fully confirmed. Factors affecting the growth of the tadpoles were investigated in detail, growth being assessed by measurements of total length. London tap water is a quite satisfactory medium if certain precautions are taken, and with a reasonable density of population and a proper regulation of the food supply the water need not be changed more often than every 2 or 3 wk. Powdered dried liver was found t o be a n excellent nutrient. Combined feeding and density of population experiments showed that optimal growth was produced when the allowance of liver powder was 2 t o 4 mg. per tadpole per day and the number of tadpoles did not exceed 8 per L. Round containers gave better results than rectangular ones, and deep ones better than shallow ones. The size of the containers, within the limits tested, was not a n important factor in growth. IJnder good conditions, the tadpoles and, after metamorphosis, the young toads can be reared with little loss. The premature metamorphic changes induced in Xenopus tadpoles by exposure to thyroid preparations and related substances are described, and their suitability for assay purposes discussed. The premature eruption of the front legs, which in Xenopus, unlike Rana, does not disturb the respiratory nicchanism, appeared to be the most suitable criterion of thyroidal activity and was used as the basis of an assay method. The following variables were considered in relation to the test: method of administration of active substance, concentration in relatioil to ahsolute amount of dose, duration of treatment, t iinc of assessing response, sizc and age nf tadpole, and temperature. Of thrsc, temperature and duration of treatment are thr most important factors. In the method finally evolved, 5 tadpoles, 18 to 25 mni. in length are placed in 200 ml. of water in a 250-1111, beaker, t o which the given dose of the substance t o be tested has been added as a fine suspension. After 3 days the tadpoles are changed to tap water and the response is assessed a t the end of the 7th day, as the percentage of tadpolcs showing eruption of 1 or both front legs. Groups of 10 or 20 tadpoles (2 or 4 beakers) were used at each dose level, and the results examined by the statistical method usually applied to such quanta1 responses. As with other biological assays, it is necessary to use a reference preparation, in terms of which the activ'

ity of the unknown specimens can be expressed. Dried thyroid powder, thyroxine, artificially iodinated proteins, and di-iodotyrosine are all active i.1 this test. Inorganic iodine, dibromotyrosinc. and dichlorotyrosine are inactive.-R. DEANESLY and A. S. PARKES.Ibid., 324-55. M. Biological Activity of Iodmated Proteins. Twelve preparations of iodinated ox blood plasma, 12 of iodinated groundnut protein (Ardein), and 18of iodinated casein were examined for biological activity in the tadpole metamorphosis test. The activity varied from negligible t o greater than that of the ordinary commercial specimen of dried thyroid gland. I n 8 preparations tested on both species relative capacity t o induce premature metamorphosis in tadpoles corresponded closely t o relative capacity t o stimulate milk yield in cows. The relationship between biological activity and acid-insoluble iodine is influenced by the method of iodination and probably by the type of protein iodinated; with casein preparations iodinated by thesame method therelationship is certainly not linear and is probably sigmoid. With the best artificially iodinated preparations so far examined the acid-insoluble iodine content is more than 10 times that of dried thyroid preparations showing the same order of biological activity. This indicates that in the artificial preparations most of the acidinsoluble iodine is not thyroxine iodine and emphasizes the need for work on the inactive substances contributing t o the total acid-insoluble iodine.-R. DEANESLY and A. S. PARKES.Ibid., 356-70.

(A. P.-C.) Isopropyl Methyl Ethers-The Anesthetic Action of. Isopropyl methyl ether has a potency of about 25% lcss than ethyl ether. I n the dog, i t produces no liver damage (bromsulfalein test). In the rat, dog, and monkey, anesthesia produced no histopathological changes in the liver and kidneys. No electrocardiographic changes were noted in the dog JR., et 01. heart or monkey heart.-JOHN C. KRANTZ, J . Phurmacol., 87, 132-37(1946) (M. W. G.) Khellinin as Coronary Dilator. Khellinin, a constituent of Ammi oisnega, dilates the coronary vesscls of thc isolated rabbit heart. The degree of coronary dilatation produced by khellinin in various concentrations (1:25,000 t o 1 :300,000) is more prniiounced if the coronary vessels arc first rendered in a state of partial spasm by barium chloride solutioii (1:40,000). Khellinin has been descirbed as a glycoside of very low toxicity, increasing the amplitude of beat of the heart and raising the blood pressure. This in addition to its pronounced action as a coronary dilator point t o the use of khellinin in theraQuart. J . P h r m . Phurpeutics.-KARAM SAYAAN. macol., 19, 135-36(1946). (S. W. G.) Lauric and Myristic Acid Ester of Colaminoformyl-Methylpyridhium Chloride (Emulsept) to the Albino Rat-The Effect of Continued Oral Administration of. Thc present paper reports on a study of the chronic toxicity of lauric and myristic acid ester of colaminoformylmethylpyridiniunichloride (I