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Medicinal Chemistry. By Wilbur J. Doran. Edited by F. F. Blicke and R. H. Cox. John Wiley & Sons, Inc., 440 Fourth Ave., New York 16, N. Y., 1959. ix + 334 pp. 14.5 × 23 cm. Price $12
60
JOURNAL OF THE
AMERICAN PHARMACEUTICAL ASSOCIATION
r
TIME (HOURS)
Fig. 1.-Electrophoretic patterns for the separation of C-14 carboxyl acetylsalicylic acid and C-14 carboxyl salicylic acid as obtained with the Forro radiochromatograph scanner, a t 60". A, acetylsalicylic acid ; S , salicylic acid.
A t 60" the breakdown is seen to occur rather rapidly. Only thirty minutes after zero time there appears a distinct curve for salicylic acid. The curves following this show a continual decrease in the amount of acetylsalicylic acid and an increase in the amount of salicylic acid. The separation was not clear cut and resulted in some overlapping of spots. Throughout this work the Rre value of acetylsalicylic acid was found to vary from 0.80 to 0.95 with the result that absolute definition of the spots often was very difficult. Such is the case here. The curves obtained for the 42' and the 25' samples are not shown here as a t both these temperatures very little hydrolysis was noticed over the fist eight hours, and the curves, for the most part, resembled those for zero time a t 60'. At 42' the appearance of a small peak for salicylic acid was f i s t noticed a t 2.50 hours. At 31.55 hours the sample was found to be almost entirely salicylic acid. A t 25" no change was noticed in the first nine hours. A t 40.53 and 59.43 hours the sample had been converted entirely t o salicylic acid, however. As mentioned previously, the results obtained 6Tbe ratio between the distances traveled by a given compound and a reference substance contitutes the Rr value.
Vol. 49, No. 1
were qualitative only due to the difficulties encountered in the electrophoretic separations of the two compounds in question. However, despite the difficulties encountered in the separation procedure for the compounds studied here, the results obtained show that by radioisotope tracer techniques i t is possible to follow the course of breakdown of medicinal agents, and the subsequent formation of the decomposition products. This fact is a significant one since i t demonstrates the advantage of being able t o study the breakdown of a drug or chemical without knowledge of the identity of breakdown products or the mechanism of degradation. The method also lends itself t o the rapid determination of degradation products at a n early stage in the decomposition. These factors combined with the ability to analyze for submicrogram quantities, even in complex mixtures, make this method of approach to the study of drug and chemical stability one which should have wide application in the future. SUMMARY
A method of electrophoretic separation and identification was developed for the products of the thermal degradation of acetylsalicylic acid. The procedure, however, as used in this work was not quantitative. Experiments were performed to determine the progress of the thermally increased hydrolysis of acetylsalicylic acid by means of radioisotope tracer techniques. The use of radioisotopic tracers as a method of stability study was shown to have the advantages of being able t o detect the most minute amounts of breakdown products, even in complex mixtures. I t is also possible t o determine the rate of breakdown without identifying the breakdown products or knowing the mechanism of degradation. REFERENCES (1) Garrett, E. R., and Carper, R . F.,
THISJOURNAL,
44, 515(1955). (2) Richter, G . N., "Laboratory Manual of Elementary Organic Chemistry," 2nd Ed., John Wiley & Sons,New York. N. Y.. 1951. (3) Conway, B. E., "Electrochemical Data," Elsevier Publishing Co., New York, N. Y . , 1952, p. 212. (-I) Conway. B. B . , ibid., p. 208.
Book Notices Medicinal Chemistry. By WILBUR J. DORAN. Edited by F. F. Blicke and R. H. Cox. John Wiley & Sons, Inc., 440 Fourth Ave., New York 16, N. Y., 1959. ix 334 pp. 14.5 x 23 cm. Price $12. In this fourth volume of a series of reviews prepared under the auspices of the Division of Medicinal Chemistry of the American Chemical Society a complete review of barbiturates, from their discovery to their present use as intravenous anesthetics, is competently presented. The review begins with the historical development of barbiturates followed by chapters dealing with the chemistry and pharmacology of these important medicinal chemicals. By the skillful use of 238 tables, an immense body of chemical data relating t o all derivatives of barbituric acid is presented. The author and editors cite more than 1,200 ref-
+
erences to the original literature. The value of the review is enhanced by a Formula Index t o all compounds appearing in the Tables 1-230, with the exception of Tables 4-7 and 9-13. This Formula Index follows the same pattern as a Chemical Abstracts formula index. Haemorrhugic Nephroso-Nephritis. By A. A. SMORODINTSEV, Y. G. CHUDAKOV. and A. V. CHURILOV.Translated by Catherine Matthews. Pergamon Press Inc.. 122 East 55th St., New York 22, N. Y., 1959. 124 pp. 14 x 21.5 cm. Price 60s. net. This monograph is devoted to modern data concerning the etiology, epidemiology, clinical features, and pathological anatomy of haemorrhagic nephroso-nephritis by three authors whose systematic investigations qualified them as authorities on the disease.
JOURNAL OF THE
AMERICAN PHARMACEUTICAL ASSOCIATION
r
TIME (HOURS)
Fig. 1.-Electrophoretic patterns for the separation of C-14 carboxyl acetylsalicylic acid and C-14 carboxyl salicylic acid as obtained with the Forro radiochromatograph scanner, a t 60". A, acetylsalicylic acid ; S , salicylic acid.
A t 60" the breakdown is seen to occur rather rapidly. Only thirty minutes after zero time there appears a distinct curve for salicylic acid. The curves following this show a continual decrease in the amount of acetylsalicylic acid and an increase in the amount of salicylic acid. The separation was not clear cut and resulted in some overlapping of spots. Throughout this work the Rre value of acetylsalicylic acid was found to vary from 0.80 to 0.95 with the result that absolute definition of the spots often was very difficult. Such is the case here. The curves obtained for the 42' and the 25' samples are not shown here as a t both these temperatures very little hydrolysis was noticed over the fist eight hours, and the curves, for the most part, resembled those for zero time a t 60'. At 42' the appearance of a small peak for salicylic acid was f i s t noticed a t 2.50 hours. At 31.55 hours the sample was found to be almost entirely salicylic acid. A t 25" no change was noticed in the first nine hours. A t 40.53 and 59.43 hours the sample had been converted entirely t o salicylic acid, however. As mentioned previously, the results obtained 6Tbe ratio between the distances traveled by a given compound and a reference substance contitutes the Rr value.
Vol. 49, No. 1
were qualitative only due to the difficulties encountered in the electrophoretic separations of the two compounds in question. However, despite the difficulties encountered in the separation procedure for the compounds studied here, the results obtained show that by radioisotope tracer techniques i t is possible to follow the course of breakdown of medicinal agents, and the subsequent formation of the decomposition products. This fact is a significant one since i t demonstrates the advantage of being able t o study the breakdown of a drug or chemical without knowledge of the identity of breakdown products or the mechanism of degradation. The method also lends itself t o the rapid determination of degradation products at a n early stage in the decomposition. These factors combined with the ability to analyze for submicrogram quantities, even in complex mixtures, make this method of approach to the study of drug and chemical stability one which should have wide application in the future. SUMMARY
A method of electrophoretic separation and identification was developed for the products of the thermal degradation of acetylsalicylic acid. The procedure, however, as used in this work was not quantitative. Experiments were performed to determine the progress of the thermally increased hydrolysis of acetylsalicylic acid by means of radioisotope tracer techniques. The use of radioisotopic tracers as a method of stability study was shown to have the advantages of being able t o detect the most minute amounts of breakdown products, even in complex mixtures. I t is also possible t o determine the rate of breakdown without identifying the breakdown products or knowing the mechanism of degradation. REFERENCES (1) Garrett, E. R., and Carper, R . F.,
THISJOURNAL,
44, 515(1955). (2) Richter, G . N., "Laboratory Manual of Elementary Organic Chemistry," 2nd Ed., John Wiley & Sons,New York. N. Y.. 1951. (3) Conway, B. E., "Electrochemical Data," Elsevier Publishing Co., New York, N. Y . , 1952, p. 212. (-I) Conway. B. B . , ibid., p. 208.
Book Notices Medicinal Chemistry. By WILBUR J. DORAN. Edited by F. F. Blicke and R. H. Cox. John Wiley & Sons, Inc., 440 Fourth Ave., New York 16, N. Y., 1959. ix 334 pp. 14.5 x 23 cm. Price $12. In this fourth volume of a series of reviews prepared under the auspices of the Division of Medicinal Chemistry of the American Chemical Society a complete review of barbiturates, from their discovery to their present use as intravenous anesthetics, is competently presented. The review begins with the historical development of barbiturates followed by chapters dealing with the chemistry and pharmacology of these important medicinal chemicals. By the skillful use of 238 tables, an immense body of chemical data relating t o all derivatives of barbituric acid is presented. The author and editors cite more than 1,200 ref-
+
erences to the original literature. The value of the review is enhanced by a Formula Index t o all compounds appearing in the Tables 1-230, with the exception of Tables 4-7 and 9-13. This Formula Index follows the same pattern as a Chemical Abstracts formula index. Haemorrhugic Nephroso-Nephritis. By A. A. SMORODINTSEV, Y. G. CHUDAKOV. and A. V. CHURILOV.Translated by Catherine Matthews. Pergamon Press Inc.. 122 East 55th St., New York 22, N. Y., 1959. 124 pp. 14 x 21.5 cm. Price 60s. net. This monograph is devoted to modern data concerning the etiology, epidemiology, clinical features, and pathological anatomy of haemorrhagic nephroso-nephritis by three authors whose systematic investigations qualified them as authorities on the disease.