New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone: studies on their metabolism in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS and their detectability in urine

3-Bromomethcathinone (3-BMC) and 3-Fluoromethcathinone (3-FMC) are two new designer drugs, which were seized in Israel during 2009 and had also appeared on the illicit drug market in Germany. These two compounds were sold via the Internet as so-called bath salts or plant feeders. The aim of the present study was to identify for the first time the 3-BMC and 3-FMC Phase I and II metabolites in rat urine and human liver microsomes using GCMS and LChigh-resolution MS (HR-MS) and to test for their detectability by established urine screening approaches using GCMS or LCMS. Furthermore, the human cytochrome-P450 (CYP) isoenzymes responsible for the main metabolic steps were studied to highlight possible risks of consumption due to drugdrug interaction or genetic variations. For the first aim, rat urine samples were extracted after and without enzymatic cleavage of conjugates. The metabolites were separated and identified by GCMS and by LCHR-MS. The main metabolic steps were N-demethylation, reduction of the keto group to the corresponding alcohol, hydroxylation of the aromatic system and combinations of these steps. The elemental composition of the metabolites identified by GCMS could be confirmed by LCHR-MS. Furthermore, corresponding Phase II metabolites were identified using the LCHR-MS approach. For both compounds, detection in rat urine was possible within the authors' systematic toxicological analysis using both GCMS and LCMSn after a suspected recreational users dose. Following CYP enzyme kinetic studies, CYP2B6 was the most relevant enzyme for both the N-demethylation of 3-BMC and 3-FMC after in vitroin vivo extrapolation. Copyright (C) 2012 John Wiley & Sons, Ltd.