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苯环己哌啶类物质甲胺酮体外代谢研究

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新型苯环己哌啶类药物的滥用现象威胁着社会安全,其中2-甲基-去氯氯胺酮(甲胺酮)作为一种新兴物质,其代谢途径和生物标志物尚未明确。本文通过建立人肝微粒体模型并应用超高效液相色谱-串联质谱技术,深入研究了甲胺酮的体外代谢途径及产物。结果表明,甲胺酮可发生脱氢、脱氨、羟基化、去甲基化等多种代谢反应,产生8种代谢产物。结合滥用者毛发样本的实际检测,确定6种代谢物的存在。通过与肝微粒体体外模型中的代谢产物相比,甲胺酮的代谢物M3。1和M4。1丰度较高,可以作为甲胺酮吸食的生物标志物。5份甲胺酮滥用者毛发样本由杭州市公安局禁毒支队提供,阴性毛发样本由本实验室志愿者提供并均经志愿者知情同意。研究结果为甲胺酮及其代谢物的检验鉴定提供了科学依据,同时也为苯环己哌啶类新精神活性物质的代谢机制研究提供了重要支持,对新精神活性物质滥用问题具有重要意义。
Investigation of metabolites of 2-methyl-dechloroketamine in vitro
The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety.The novel psychoactive substance 2-methyl-deschloroketamine(2-MDCK),belonging to the phenylcyclohexylpyridine class,has recently surfaced as a new compound.However,there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers.In this study,a human liver microsomal model was established,and ultra-high-performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)technology was applied to investigate the in vitro metabolism and products of 2-MDCK.The results indicate that 2-MDCK undergoes various metabolic reactions,including dehydrogenation,deamination,hydroxylation,and demethylation,leading to the formation of eight metabolites.By conducting actual testing on hair samples from 2-MDCK abusers,the existence of six metabolites was confirmed.Comparing the metabolic products in the liver microsomal in vitro model,M3.1 and M4.1 were identified as biomarkers for 2-MDCK consumption.Five samples of abusers of 2-methyl-dechloroketamine were provided by the Anti-Drug Brigade of the Hangzhou Public Security Bureau.Negative hair samples were provided by laboratory volunteers,and all samples were obtained with the informed consent of the volunteers.These findings provide a scientific basis for the detection and identification of 2-MDCK and its metabolites,as well as crucial support for the study of the metabolic mechanisms of similar novel psychoactive substances in the phenylcyclohexylpyridine class.This research holds significant importance in addressing the issue of abuse of new psychoactive substances.

2-methyl-deschloroketamineliver microsomehairmetabolitemetabolic pathway

茹俊辉、黄峰、吴昊、王旻昊、柯星、高建红、范一雷

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浙江警察学院浙江省毒品防控技术研究重点实验室,浙江杭州 310053

浙江迪安司法鉴定中心,浙江杭州 310007

国家毒品实验室浙江分中心浙江省禁毒和毒情监测关键技术研究重点实验室,浙江杭州 310053

甲胺酮 肝微粒体 毛发 代谢产物 代谢途径

浙江省自然科学基金浙江省自然科学基金国家级大学生创新创业训练计划

LTGC23H230001LTGC23B050003202211483025

2024

药学学报
中国药学会 中国医学科学院药物研究所

药学学报

CSTPCD北大核心
影响因子:1.274
ISSN:0513-4870
年,卷(期):2024.59(5)