A Note on the Estimation of Isonicotinic Acid Hydrazide

Abstract

THE current interest in isonicotinic acid hydrazide has prompted the need for a rapid assay method. It is well known that hydrazines in slightly alkaline solutions are oxidised by iodine according to the scheme :-Mono-acylhydrazides are said to behave in a different way1 :-However, isonicotinic acid hydrazide consumes 4 equivalents of iodine when oxidised as described below. Thus the mechanism of the reaction seems to be analogous to that of hydrazines.Isonicotinic acid hydrazide may be titrated in the following manner :-Dissolve 50 mg. of the substance in 50 ml. of water, add 1 g. of sodium bicarbonate and 25 ml. of 0.1N iodine. Allow to stand for 15 minutes. Cautiously add 10 ml. of 5N hydrochloric acid and titrate the excess of iodine with 0: 1N sodium thiosulphate using starch solution as indicator. 1 ml. of 0-1N iodine corresponds to 0.003429 g. of C,H,ON,.Two samples of the hydrazide from different manufacturers, m.pt. 168" to 169" C. and 170" to 171" C. (Kofler), assayed 97.8,97.8,98.0 and 98.4, 98.6, 98.7, 98.2 per cent.Commercial tablets containing 50 mg. of the hydrazide were analysed in a similar way, the only difference being that the suspension of the tablet powder was centrifuged before the addition of the sodium bicarbonate. The following results were obtained :--47.7, 48.1, 48.3 and 48.2 mg. per tablet.

High-Performance Liquid Chromatographic Analysis of Isoniazid and Its Dosage Forms

“…One analysis is based on the addition of excess standard iodine followed by back-titration with standard thiosulfate (1). This procedure was official in four USP revisions but was supplanted in the current USP XIX (2) by a nitrous acid titration similar to that used for the determination of sulfa drugs.…”

Indirect Nonaqueous Titration of Hydrochlorides of Nitrogenous Bases

“…This method has proved to be efficient for eliminating halide-ion interference and, therefore, has been adopted by many official compendia for the determination of the hydrochlorides of nitrogenous bases. The method has also been applied to the determination of some alkaloid halides (5,6), using 0.01 N perchloric acid solution as the titrant and crystal violet as the indicator, and the hydrochlorides of several antihistamines (7) by potentiometric titration against standard tosylic acid solution in chloroform. The hydrochlorides of some phenothiazine derivatives were also determined (8) either in acetone using a mercuric acetate reagent or in a mixture of hexane and acetone after extracting the base from an aqueous potassium hydroxide solution.…”