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Colorimetric determination of some pharmaceutical primary aromatic amines
290
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SHORT
acetylene flame. They are in agreement reported by Flanagan.’ ’
with
values
REFERENCES
Analytical Methods for Atomic Absorption Spectrophotometry, Perkin-Elmer Corporation, 1976. Analytical Methods for Flame Spectroscopy, Varian Techtron, 1972. .I. Ramirez-Muhoz, Talanta, 1973, 20, 705. A. S. de Endredy, Clay Minerals, 1963, 5, 218.
Juhru.Vol.25.pp.290-291 0 Pcrgamon Press Ltd.. 197X. Printed
5. 0. P. Mehra and M. L. Jackson, 7th Natl. Conf. on Clays and Clay Minerals, 1960, 317. 6. D. D. Coffin, Can. J. Soil. Sci., 1963, 1. I. H. H. Le Riche, Geoderma, 1977, 18, 279. 8. Y. La Flamme, At. Abs. Newsletter, 1968, 7, 101. 9. P. M. Huang, M. K. Wang, M. H. Wu, C. L. Liu and T. S. C. Wang, Geoderma, 1977, 18, 251. 10. H. J. Rosler, Geochemical Tables, Elsevier, New York, 1972. 11. F. J. Flanagan, U.S. Geol. Survey Prof: Paper 840, 1976, p. 131.
0039-9140/78/0501-0?90u)2.00/0 in Great Britain.
COLORIMETRIC PHARMACEUTICAL
DETERMINATION OF SOME PRIMARY AROMATIC AMINES
and S. A. SOLIMAN Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Egypt
S. BELAL,ELSAYED, A. ELNENAEY
Department of Pharmaceutical
(Received 28 September 1976. Revised 2 December 1977. Accepted 12 January 1978)
Summary-A method for determination of amines of pharmaceutical of the amine and coupling of the product with ethyl acetoacetate.
Photometric methods for the determination of primary aromatic amines are of great interest to the pharmaceutical analyst, owing to their high sensitivity and &de applicabilitv. The most widelv used are based on counlina the diazoti&d amines with phenols and amine%‘-* A This coupling reaction, being an electronhilic substitution, may also &cur with carbaiions associ&+ with active hydrogen, such as ethyl acctoacetate. A calorimetric method for the determination of acetoacetic acid has been based on the coloured product given with diazotized 4-nitroaniline.5.6 In the present work this reaction is applied to the determination of some primary aromatic amines. EXPERIMENTAL Reagents Erhylacetoacetate solution in ethanol, 3% v/v. Standard solutions of the drugs investigated. Stock solu-
tions were prepared in O.lM hydrochloric acid to contain 1 mg of the drug per ml, a few ml of ethanol being added to aid dissolution when necessary. Working standards were prepared by diluting the stock standards with O.lM hydrochloric acid [to give O.OOSo/,for all drugs except for p-aminpberuoic acid (0.0020/,)1.
Transfer
0.02-0.1 mg
OH0 CH ~~_;--COOEt
3
I
ri
of
p-aminobenzoic
acid
OH0 -H+ OH-
!
or
solution, and cool in an ice-bath for 3 min. Add 2 ml 01 2% urea solution, shake, and allow to stand for 2min. Add 1 ml of ethyl acetoacetate solution, and 2ml of 200/, sodium hydroxide solution. Shake well and dilute to volume with water. Measure the absorbance in a l-cm cell against a reagent blank at the wavelength of maximum absorption (Tible 1). Eye drops and injections. The preparation is suitably diluted with O.lM hydrochloric acid to give a concentration of about O.OOSO,<. A suitable portion of this solution is treated as described above. Tablets. A SOO-mg portion of the powdered tablets is extracted by shaking with five successive 25-ml portions of 1M hydrochloric acid, the extracts being filtered into a 250-m] standard flask and diluted to volume with water. An appropriate portion is then treated as above. Ointment. A suitable weight of ointment is shaken with 20mI of petroleum ether (4060”) in a separatory funnel and then extracted with four portions of 5ml of ethanol plus 10ml of 1M hydrochloric acid. The aqueous extracts are transferred to a lOO-ml standard flask and diluted to volume, then the assay is completed as described above. RESULTS AND DlSCUSSlON
The amines tested were procaine hydrochloride, p-aminobenzoic acid, p-aminosalicylic acid, benzocaine and suiphacetamide sodium. The coupling reaction OH0
//
) CH,-C-C-C-COOEt 8
0.050.35 mg of p-aminosalicylic acid, benzocaine or proCaine hydrochloride, or 0.025-0.25 mg of sulphacetamide sodium, or a suitable portion of a pharmaceutical preparation, into a 25-ml standard flask. Add 1 ml of 1M hydrochloric acid, followed by 1ml of 3% sodium nitrite
interest is based on diazotization
II
%
I,
CH,-c--CC-COOEt
I h-N--Are is instantaneous, and yellow products are formed. The amine is diazotized with excess of nitrous acid, but the surplus affects the stability of the colour and must be removed with urea, which has no effect on the products. The coupling reagent is then added as its ethanolic or methanolic solution, 1 ml of 3% solution being adequate.
291
SHORTCOMMtJNlCATlONS Table. 1. Absorption maxima and EfC of the coloured products obtained from the drugs tested I, max,
Compound
nm
Et% I.Xn
Procaine hydrochloride Benzocaine Sulphacetamide sodium p-Aminobenzoic acid p-Aminosalicylic acid
365 385 405 365 360
700 700 967 1564 500
Table 2. Determination
of the test amines in pharmaceutical
preparations*
Recovery Pharmaceutical
preparation
Procaine hydrochloride injection Sulphacetamide eye drops p-Aminobenxoic acid tablets p-Aminosalicylic acid tablets Benzocaine ointment
B.P. 1973 method’
Proposed method
98.8 98.1 98.7 97.5 97.2
99.0 97.6 98.3 98.7 97.9
k f k f f
0.2 0.3 0.4 0.4 0.2
* f f k f
0.4 0.7 0.2 0.3 0.2
* Means of 5 experiments f standard deviation
The concentration of the alkali used in the coupling reaction affects the accuracy. The most intense colour is obtained when the final sodium hydroxide concentration is about 0.4M. Lower concentrations give incomplete colour development, and higher ones tend to decrease the stability of the colour. The absorption maxima are in the region 365-405nm. The E:$m values are shown in Table 1. Beer’s law is obeyed for these amines in the concentration range 0.002-0.015mg/ml. The sensitivity is about the same as that of the other calorimetric methods. Common tablet excipients and additives which usually accompany these drugs in pharmaceuticals do not interfere, and the procedure was successfully applied to analysis of pharmaceutical preparations. The recoveries obtained were satisfactory and in reasonable agreement with those obtained by the B.P. 1973 method (Table 2).
Tahra Vol. 25. pp. 2Y I-293 @ Pergamon Press Ltd.. 1978.
REFERENCES
1. F. J. Bandelin and C. R. Kemp, Ind. Eng. Chem., Anal. Ed., 1946, 18, 470. 2. W. Eissner, Arch. Pharm., 1934 268, 322. 3. D. T. Englis and H. A. Fiess. Ind. Eng. Chem., 1944, 36,604. 4. A. C. Bratton and E. K. Marshall Jr., 1. Biol. Chem., 1939, 128, 537. 5. M. S. Rosenthal, ibid., 1949, 179, 1235. 6. T. E. Friedemann and G. E. Haugen, ibid., 1943, 147, 415. 7. British Pharmacopoeia, 1973, p. 446. Pharmaceutical Press, London.
003Y-904l/7x/050l42YI Printed in Great Britam
ALKALIMETRIC DETERMINATION OF MERCAPTANS TRITHIOCARBONIC ACID FORMATION
THROUGH
BALBIRCHAND VERMAand SWATANTARKUMAR Department of Chemistry, Himachal Pradesh University, Simla-171005, India (Received 6 June 1977. Accepted I8 November 1977)
Summary-A simple and rapid alkalimetric method for the determination of mercaptans through trithiocarbonic acid formation is described. The mercaptans are titrated in tert.-butanol in the presence of carbon disulphide with standard aqueous sodium hydroxide, with phenolphthalein as indicator. The - SH group is smoothly, rapidly and quantitatively transformed into the -S-C-SNa II S group under the specified conditions. The method has been extended to the analysis of mercaptancarboxylic acid and mercaptan-trithiocarbonate mixtures.
$wm/ll
COMMUNICATIONS
SHORT
acetylene flame. They are in agreement reported by Flanagan.’ ’
with
values
REFERENCES
Analytical Methods for Atomic Absorption Spectrophotometry, Perkin-Elmer Corporation, 1976. Analytical Methods for Flame Spectroscopy, Varian Techtron, 1972. .I. Ramirez-Muhoz, Talanta, 1973, 20, 705. A. S. de Endredy, Clay Minerals, 1963, 5, 218.
Juhru.Vol.25.pp.290-291 0 Pcrgamon Press Ltd.. 197X. Printed
5. 0. P. Mehra and M. L. Jackson, 7th Natl. Conf. on Clays and Clay Minerals, 1960, 317. 6. D. D. Coffin, Can. J. Soil. Sci., 1963, 1. I. H. H. Le Riche, Geoderma, 1977, 18, 279. 8. Y. La Flamme, At. Abs. Newsletter, 1968, 7, 101. 9. P. M. Huang, M. K. Wang, M. H. Wu, C. L. Liu and T. S. C. Wang, Geoderma, 1977, 18, 251. 10. H. J. Rosler, Geochemical Tables, Elsevier, New York, 1972. 11. F. J. Flanagan, U.S. Geol. Survey Prof: Paper 840, 1976, p. 131.
0039-9140/78/0501-0?90u)2.00/0 in Great Britain.
COLORIMETRIC PHARMACEUTICAL
DETERMINATION OF SOME PRIMARY AROMATIC AMINES
and S. A. SOLIMAN Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Egypt
S. BELAL,ELSAYED, A. ELNENAEY
Department of Pharmaceutical
(Received 28 September 1976. Revised 2 December 1977. Accepted 12 January 1978)
Summary-A method for determination of amines of pharmaceutical of the amine and coupling of the product with ethyl acetoacetate.
Photometric methods for the determination of primary aromatic amines are of great interest to the pharmaceutical analyst, owing to their high sensitivity and &de applicabilitv. The most widelv used are based on counlina the diazoti&d amines with phenols and amine%‘-* A This coupling reaction, being an electronhilic substitution, may also &cur with carbaiions associ&+ with active hydrogen, such as ethyl acctoacetate. A calorimetric method for the determination of acetoacetic acid has been based on the coloured product given with diazotized 4-nitroaniline.5.6 In the present work this reaction is applied to the determination of some primary aromatic amines. EXPERIMENTAL Reagents Erhylacetoacetate solution in ethanol, 3% v/v. Standard solutions of the drugs investigated. Stock solu-
tions were prepared in O.lM hydrochloric acid to contain 1 mg of the drug per ml, a few ml of ethanol being added to aid dissolution when necessary. Working standards were prepared by diluting the stock standards with O.lM hydrochloric acid [to give O.OOSo/,for all drugs except for p-aminpberuoic acid (0.0020/,)1.
Transfer
0.02-0.1 mg
OH0 CH ~~_;--COOEt
3
I
ri
of
p-aminobenzoic
acid
OH0 -H+ OH-
!
or
solution, and cool in an ice-bath for 3 min. Add 2 ml 01 2% urea solution, shake, and allow to stand for 2min. Add 1 ml of ethyl acetoacetate solution, and 2ml of 200/, sodium hydroxide solution. Shake well and dilute to volume with water. Measure the absorbance in a l-cm cell against a reagent blank at the wavelength of maximum absorption (Tible 1). Eye drops and injections. The preparation is suitably diluted with O.lM hydrochloric acid to give a concentration of about O.OOSO,<. A suitable portion of this solution is treated as described above. Tablets. A SOO-mg portion of the powdered tablets is extracted by shaking with five successive 25-ml portions of 1M hydrochloric acid, the extracts being filtered into a 250-m] standard flask and diluted to volume with water. An appropriate portion is then treated as above. Ointment. A suitable weight of ointment is shaken with 20mI of petroleum ether (4060”) in a separatory funnel and then extracted with four portions of 5ml of ethanol plus 10ml of 1M hydrochloric acid. The aqueous extracts are transferred to a lOO-ml standard flask and diluted to volume, then the assay is completed as described above. RESULTS AND DlSCUSSlON
The amines tested were procaine hydrochloride, p-aminobenzoic acid, p-aminosalicylic acid, benzocaine and suiphacetamide sodium. The coupling reaction OH0
//
) CH,-C-C-C-COOEt 8
0.050.35 mg of p-aminosalicylic acid, benzocaine or proCaine hydrochloride, or 0.025-0.25 mg of sulphacetamide sodium, or a suitable portion of a pharmaceutical preparation, into a 25-ml standard flask. Add 1 ml of 1M hydrochloric acid, followed by 1ml of 3% sodium nitrite
interest is based on diazotization
II
%
I,
CH,-c--CC-COOEt
I h-N--Are is instantaneous, and yellow products are formed. The amine is diazotized with excess of nitrous acid, but the surplus affects the stability of the colour and must be removed with urea, which has no effect on the products. The coupling reagent is then added as its ethanolic or methanolic solution, 1 ml of 3% solution being adequate.
291
SHORTCOMMtJNlCATlONS Table. 1. Absorption maxima and EfC of the coloured products obtained from the drugs tested I, max,
Compound
nm
Et% I.Xn
Procaine hydrochloride Benzocaine Sulphacetamide sodium p-Aminobenzoic acid p-Aminosalicylic acid
365 385 405 365 360
700 700 967 1564 500
Table 2. Determination
of the test amines in pharmaceutical
preparations*
Recovery Pharmaceutical
preparation
Procaine hydrochloride injection Sulphacetamide eye drops p-Aminobenxoic acid tablets p-Aminosalicylic acid tablets Benzocaine ointment
B.P. 1973 method’
Proposed method
98.8 98.1 98.7 97.5 97.2
99.0 97.6 98.3 98.7 97.9
k f k f f
0.2 0.3 0.4 0.4 0.2
* f f k f
0.4 0.7 0.2 0.3 0.2
* Means of 5 experiments f standard deviation
The concentration of the alkali used in the coupling reaction affects the accuracy. The most intense colour is obtained when the final sodium hydroxide concentration is about 0.4M. Lower concentrations give incomplete colour development, and higher ones tend to decrease the stability of the colour. The absorption maxima are in the region 365-405nm. The E:$m values are shown in Table 1. Beer’s law is obeyed for these amines in the concentration range 0.002-0.015mg/ml. The sensitivity is about the same as that of the other calorimetric methods. Common tablet excipients and additives which usually accompany these drugs in pharmaceuticals do not interfere, and the procedure was successfully applied to analysis of pharmaceutical preparations. The recoveries obtained were satisfactory and in reasonable agreement with those obtained by the B.P. 1973 method (Table 2).
Tahra Vol. 25. pp. 2Y I-293 @ Pergamon Press Ltd.. 1978.
REFERENCES
1. F. J. Bandelin and C. R. Kemp, Ind. Eng. Chem., Anal. Ed., 1946, 18, 470. 2. W. Eissner, Arch. Pharm., 1934 268, 322. 3. D. T. Englis and H. A. Fiess. Ind. Eng. Chem., 1944, 36,604. 4. A. C. Bratton and E. K. Marshall Jr., 1. Biol. Chem., 1939, 128, 537. 5. M. S. Rosenthal, ibid., 1949, 179, 1235. 6. T. E. Friedemann and G. E. Haugen, ibid., 1943, 147, 415. 7. British Pharmacopoeia, 1973, p. 446. Pharmaceutical Press, London.
003Y-904l/7x/050l42YI Printed in Great Britam
ALKALIMETRIC DETERMINATION OF MERCAPTANS TRITHIOCARBONIC ACID FORMATION
THROUGH
BALBIRCHAND VERMAand SWATANTARKUMAR Department of Chemistry, Himachal Pradesh University, Simla-171005, India (Received 6 June 1977. Accepted I8 November 1977)
Summary-A simple and rapid alkalimetric method for the determination of mercaptans through trithiocarbonic acid formation is described. The mercaptans are titrated in tert.-butanol in the presence of carbon disulphide with standard aqueous sodium hydroxide, with phenolphthalein as indicator. The - SH group is smoothly, rapidly and quantitatively transformed into the -S-C-SNa II S group under the specified conditions. The method has been extended to the analysis of mercaptancarboxylic acid and mercaptan-trithiocarbonate mixtures.
$wm/ll