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
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
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DOI：
10.1002/jms.2960
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发表时间：
2012-02-01
影响因子：
2.3
通讯作者：
Maurer, Hans H.
中科院分区：
文献类型：
--
作者：
Meyer, Markus R.;Vollmar, Christian;Maurer, Hans H.
3-溴甲卡西酮(3-BMC)和3-氟甲卡西酮(3-FMC)是两种新的设计毒品，2009年在以色列查获，也出现在德国的非法药物市场上。这两种化合物通过互联网以所谓的浴盐或植物饲养剂的形式出售。本研究的目的是首次利用气相色谱-质谱仪(GCMS)和高分辨毛细管电泳质谱(HR-MS)鉴定大鼠尿和人肝微粒体中的3-BMC和3-FMC的I和II相代谢物，并用GCMS或LC MS检测尿液中3-BMC和3-FMC的检测能力。此外，研究了负责主要代谢步骤的人类细胞色素-P450(CYP)同工酶，以强调由于药物相互作用或遗传变异可能导致的消费风险。对于第一个目的，提取大鼠尿样后和没有酶裂解偶联物。代谢物用气相色谱-质谱仪和薄层色谱-质谱法进行分离和鉴定。主要的代谢步骤是N-脱甲基化、酮基还原为相应的醇、芳香族体系的羟基化以及这些步骤的组合。GCMS鉴定的代谢物的元素组成可用薄层色谱-质谱法确证。此外，使用LC HR-MS方法鉴定了相应的II相代谢物。对于这两种化合物，在作者使用GCMS和LCMSN进行系统的毒理学分析后，在可疑的娱乐使用者剂量后，可以在老鼠尿液中检测到。CYP酶动力学研究表明，在体内外推算后，3-BMC和3-FMC的N-脱甲基化均与CYP2B6酶最相关。版权所有(C)2012 John Wiley&Sons，Ltd.
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.