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Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam
Author(s) -
Cabrera C. Gallardo,
de Waisbaum R. Goldberg,
Nudelman N. Sbarbati
Publication year - 2005
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.861
Subject(s) - chemistry , photodegradation , hydrolysis , photochemistry , aqueous solution , degradation (telecommunications) , solvent , kinetics , decomposition , reaction mechanism , organic chemistry , catalysis , telecommunications , physics , photocatalysis , quantum mechanics , computer science
The corresponding o ‐aminobenzophenones are usually reported as the main degradation products in the hydrolysis of 1,4‐benzodiazepinones. Nevertheless, in previous studies of diazepam ( DZ ) in acidic aqueous medium we isolated and characterized seven unexpected degradation products. Kinetic measurements under several reaction conditions shed some light on the mechanisms of the complex reactions that are taking place, and photochemical studies give hints on the mechanisms of chlorination and annelation processes. Alprazolam ( AL ) seems to exhibit an unusually high stability against hydrolysis under several conditions; nevertheless, the structure is sensitive to photolytic cleavage. The photodegradation of AL was studied in aqueous and methanolic solutions. Characterization of the isolated products by 1 H and 13 C NMR and mass spectrometry revealed that electron transfer, oxidation and rearrangement reactions take place. The influence of several variables such as pH, solvent composition and light irradiation were examined and mechanisms for the formation of three photoproducts are proposed. A specific method for the determination of AL in the presence of photoproducts was developed, which allowed kinetic determinations of the photostability of AL . The photosensitivity observed in some patients treated with AL seems to be due to one of the characterized photoproducts. Copyright © 2004 John Wiley & Sons, Ltd.