Looking at flubromazolam metabolism from four different angles: Metabolite profiling in human liver microsomes, human hepatocytes, mice and authentic human urine samples with liquid chromatography high-resolution mass spectrometry (original) (raw)

Forensic science international, 2016

Abstract

Flubromazolam is a triazolam benzodiazepine that recently emerged as a new psychoactive substance. Since metabolism data are scarce and good analytical targets besides the parent are unknown, we investigated flubromazolam metabolism in vitro and in vivo. 10μmol/L flubromazolam was incubated with human liver microsomes for 1h and with cryopreserved human hepatocytes for 5h. Mice were administered 0.5 or 1.0mg flubromazolam/kg body weight intraperitoneally, urine was collected for 24h. All samples, together with six authentic forensic human case specimens, were analyzed (with or without hydrolysis, in case it was urine) by UHPLC-HRMS on an Acquity HSS T3 column with an Agilent 6550 QTOF. Data mining was performed manually and with MassMetasite software (Molecular Discovery). A total of nine metabolites were found, all generated by hydroxylation and/or glucuronidation. Besides O-glucuronidation, flubromazolam formed an N(+)-glucuronide. Flubromazolam was not metabolized extensively in ...

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