REACTIONS OF TEMAZEPAM IN ACIDIC AQUEOUS-SOLUTION VIA OXYGEN-18-LABELED PRODUCT ANALYSIS BY MASS-SPECTROMETRY

Temazepam, a hypnotic and anxiolytic drug, is inactivated by hydrolysi s in acidic aqueous solutions including simulated gastric fluid. React ion products formed in acidic oxygen-18 water were characterized by el ectron impact and/or chemical ionization mass spectral analysis. Temaz epam remaining in the reaction mixture contained either one or two oxy gen-18 atoms. The most abundant hydrolysis product l-4'-chloro-N-methy l-2-amino-2-hydroxyacetanilide) was found to contain either one or two oxygen-18 atoms and the minor hydrolysis product (2-methylamino-5-chl orobenzophenone) had one oxygen-18 atom. The benzophenone oxygens of t he hydrolysis products underwent both acid- and base-catalyzed oxygen exchange with solvent water. The C2 carbonyl carbon of temazepam under went an essentially irreversible nucleophilic attack by water in stron gly acidic aqueous media to form a hydrate. The results not only provi ded additional evidence for the mechanism of acid-catalyzed hydrolysis , but also revealed some heretofore unknown acid-catalyzed reactions o f temazepam.