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首页> 外文期刊>Journal of mass spectrometry: JMS >Low resolution and high resolution MS for studies on the metabolism and toxicological detection of the new psychoactive substance methoxypiperamide (MeOP)
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Low resolution and high resolution MS for studies on the metabolism and toxicological detection of the new psychoactive substance methoxypiperamide (MeOP)

机译：低分辨率和高分辨率质谱仪，用于研究新型精神活性物质甲氧基哌酰胺（MeOP）的代谢和毒理学检测

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摘要

In 2013, the new psychoactive substance methoxypiperamide (MeOP) was first reported to the European Monitoring Centre for Drug and Drug Addiction. Its structural similarity to already controlled piperazine designer drugs might have contributed to the decision to offer MeOP for online purchase. The aims of this work were to identify the phase I/II metabolites of MeOP in rat urine and the human cytochrome P450 (CYP) isoenzymes responsible for the initial metabolic steps. Finally, the detectability of MeOP in rat urine by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography coupled with multistage mass spectrometry (LC-MSn) standard urine screening approaches (SUSAs) was evaluated. After sample preparation by cleavage of conjugates followed by extraction for elucidating phase I metabolites, the analytes were separated and identified by GC-MS as well as liquid chromatography-high resolution-tandem mass spectrometry (LC-HR-MS/MS). For detection of phase II metabolites, the analytes were separated and identified after urine precipitation followed by LC-HR-MS/MS. The following metabolic steps could be postulated: hydrolysis of the amide, N-oxide formation, N- and/or O-demethylation, oxidation of the piperazine ring to the corresponding keto-piperazine, piperazine ring opening followed by oxidation of a methylene group to the corresponding imide, and hydroxylation of the phenyl group. Furthermore, N-acetylation, glucuronidation and sulfation were observed. Using human CYPs, CYP1A2, CYP2C19, CYP2D6, and/or CYP3A4 were found to catalyze N-oxide formation and N-, O-demethylation and/or oxidation. Mostly MeOP and N-oxide-MeOP but to a minor degree also other metabolites could be detected in the GC-MS and LC-MSn SUSAs. Copyright (c) 2015 John Wiley & Sons, Ltd.
机译：2013年，新的精神活性物质甲氧基哌酰胺（MeOP）首次向欧洲药物和药物成瘾监测中心报告。它与已经控制的哌嗪设计药物的结构相似性可能有助于决定提供MeOP在线购买。这项工作的目的是确定大鼠尿液中MeOP的I / II期代谢物和负责初始代谢步骤的人细胞色素P450（CYP）同工酶。最后，通过气相色谱-质谱（GC-MS）和液相色谱-多级质谱（LC-MSn）标准尿液筛选方法（SUSAs）评价了大鼠尿液中MeOP的可检测性。通过裂解缀合物制备样品，然后进行提取以阐明I相代谢物后，分离出分析物，并通过GC-MS以及液相色谱-高分辨率串联质谱（LC-HR-MS / MS）进行鉴定。为了检测II期代谢物，尿液沉淀后再进行LC-HR-MS / MS分离并鉴定分析物。可以假设以下代谢步骤：酰胺水解，N-氧化物形成，N-和/或O-去甲基化，哌嗪环氧化为相应的酮-哌嗪，哌嗪环打开，随后亚甲基氧化为相应的酰亚胺，以及苯基的羟基化。此外，观察到N-乙酰化，葡糖醛酸化和硫酸化。发现使用人CYP CYP1A2，CYP2C19，CYP2D6和/或CYP3A4可以催化N-氧化物的形成以及N-，O-去甲基化和/或氧化。 GC-MS和LC-MSn SUSAs大多检测到MeOP和N-氧化物-MeOP，但也有少量代谢物。版权所有（c）2015 John Wiley＆Sons，Ltd.

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