METABOLIC PROFILE AND MECHANISMS OF GABA-TARGETED RECEPTOR PROPOXAZEPAM METABOLIZATION IN HUMAN HEPATOCYTES

The aim of this study was to identify the Propoxazepam metabolites, formed by suspension of cryopreserved human hepatocytes, using the precise method of mass LC-MS/MS analysis. Methods. A suitable chromatographic method was developed for the profiling of Propoxazepam and its metabolites. Samples were analyzed using a Waters Vion high resolution LC-MS/MS instrument, and data were examined using Waters Unifi software to determine the identity of the most abundant metabolites. Following a 4-hour incubation with human hepatocytes, intact Propoxazepam molecule accounted for 96.0% of the profile. Its most abundant metabolite was the oxidize. Results. Propoxazepam (3-hydroxyderivative), which accounted for approximately 2.5% of the total peak response in the 4-hour sample. Two minor components were also found, each accounting for < 10% of the total peak response. Glucuronic conjugates have not been found under the experimental conditions. All metabolites formed represented less than 10% of the total chromatographic peak response. Coclusion. The data obtained indicate the absence of reactive electrophilic derivatives among the metabolites of Propoxazepam.