Iodometric determination of cystamine dihydrochloride in tablets using diperoxyadipic acid

Mykola Blazheyevskiy, Valeriy Moroz

Abstract

The kinetics of cystamine dihydrochloride oxidation by diperoxyadipic acid (DPAA) was studied in aqueous buffer solutions of pH 2.9, 6.9, 8.0, 8.5 and 9.2 under second-order conditions at the temperature 293 K. The second order rate constants, k (L mol−1 min−1) were calculated from kinetic values. A suitable mechanism scheme based on these observations was proposed. The possibility of application of DPAA as reagent for oxidimetric determination of cystamine dihydrochloride in tabtets was investigated. Cystamine dihydrochloride was determined by indirect titration with DPAA. The required amount of Cystamine dihydrochloride was dissolved in water, pH 8.0 buffer solution and DPAA solution was added. After 7 min, the solution was acidified. The excess DPAA was determined via iodometric titration. The advantages of the applied analytical techniques in the determination of cystamine dihydrochloride in tablets «Cystamine 0.2 g» was presented. The recovery of сystamine dihydrochloride was 99.32±1.45%. A paired t-test showed that all results obtained for bulk drug and in tablets «Cystamine 0.2 g», using the proposed procedure and the official procedure respectively, agreed at the 95% confidence level.

Keywords

kinetics; oxidation; Cystamine; assay; Diperoxyadipic acid

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References

Mashkovskiy MD. Lekarstvennyie sredstva [Medicinal products]. 16-e izd. pererab., ispravl. i dop. Moscow: Novaya volna; 2012. 1216 p.

Trohimchuk VV, Chakchir BA, Hveschuk PF, Alekseev VV. Kontrol kachestva tsistamina digidrohlorida v protsesse hraneniya [Quality control of cystamine dihydrochloride during storage]. Farmatsiya. 1985;1:33–5.

Tabletki tsistamina 0,2. Farmokopeynaya Statya. 42-237-72.

Metodicheskie ukazaniya po spektrofotometricheskomu izmereniyu kontsentratsii bis-(beta-aminoetil)-disulfida digidrohlorida (Tsistamina) v vozduhe rabochey zonyi [Methodical instructions for spectrophotometric measurement of the concentration of bis(beta-aminoethyl) disulfi de dihydrochloride (Tsystamine) in the air of the work area]. MUK 41814-99.

Sakharov A. Quantitative coulometric determination of cystamine. Pharmaceutical Chemistry Journal 1978;12(8):1094-1098. https://doi.org/10.1007/bf00778077

Ciesielski W, Skowron M. Coulometric Titration of Disulfides with Electrogenerated Chlorine. Chem Anal Wars. 2005;50:47–53.

Danevich VI, Bureneva MI. Okislitelno-vosstanovitelnoe titrovanie [Oxidation-reduction titration]. SPb.: SPHFA; 2001. 44 p.

Pinto J, Khomenko T, Szabo S, McLaren G, Denton T, Krasnikov B, Jeitner T, Cooper A. Measurement of sulfur-containing compounds involved in the metabolism and transport of cysteamine and cystamine. Regional differences in cerebral metabolism. Journal of Chromatography B 2009;877(28):3434-3441. https://doi.org/10.1016/j.jchromb.2009.05.041

Kim Y, Na D. Simultaneous Determination of Cysteamine and Cystamine in Cosmetics by Ion-Pairing Reversed-Phase High-Performance Liquid Chromatography. Toxicological Research 2019;35(2):161-165. https://doi.org/10.5487/tr.2019.35.2.161

Karandi IV, Buzlanova MM. Potentsiometricheskoe opredelenie organicheskih disulfidov s ispolzovaniem formamidinsulfinovoy kislotyi v kachestve vosstanovitelnogo agenta [Potentiometric determination of organic sulphides using formamidine sulfinic acid as a reducing agent]. Zhurnal Anal Him. 1999;54(8):848–50.

Ariëns EJ, editor. Drug Design: Medicinal Chemistry: A Series of Monographs. Vol. 6. Elsevier; 2017. 382 p.

Klayman D, Milne G. 2-Amino-Δ2-thiazolines from Aminoethyl Thiosulfates. The Mass Spectra of 2-Amino-Δ2-thiazolines and Related Compounds. The Journal of Organic Chemistry 1966;31(7):2349-2355. https://doi.org/10.1021/jo01345a064

Smith M, March J. March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6th ed. By Michael B. Smith and Jerry March . Wiley Interscience : New York. 2007 . 2357 + xx pp. £58.95 (hardback). ISBN 13 978-0-471-72091-1, ISBN 10 0-471-72091-7 .. Organic Process Research & Development 2007;11(5):924-924. https://doi.org/10.1021/op700136u

Parker W, Witnauer L, Swern D. Peroxides. IV.2Aliphatic Diperacids. Journal of the American Chemical Society 1957;79(8):1929-1931. https://doi.org/10.1021/ja01565a043