Abstract:

 Objective To detect and analyze the in vitro metabolites of AB-CHMINACA which were generated in the in vitro human liver microsomes model system by Ultra Performance Liquid Chromatography （UPLC） coupled to High Resolution Mass Spectrum （HR-MS）. And then compare the results with the urine sample with a real abuser. Methods To simulate the metabolic process in human body by establishing the in vitro human liver microsomes model， and then determine and elaborate the reaction points and pathways of metabolism by HR-MS. Results AB-CHMINACA generated 10 metabolites in the in vitro human liver microsomes model totally. Carboxamide hydrolysis， hydroxylation on the methylpropyl moiety and the combination of N-dealkylation and carboxamide hydrolysis were its main metabolic pathways. Carboxamide hydrolysis metabolite M1， hydroxylation on the methylpropyl moiety metabolite M4 and the combination of N-dealkylation and carboxamide hydrolysis metabolite M10 also appeared in the urine sample of a AB-CHMINACA abuser. Conclusion The method is fast and efficient， and it can predict the in vivo metabolites to a certain extent. So we suggest that the carboxamide hydrolysis metabolite and hydroxylation on the methylpropyl moiety metabolite can be used as biomarkers for routine analysis of urine samples.

Key words:

AB-CHMINACA, synthetic cannabinoid, high resolution mass spectrum （HR-MS）, human liver microsomes

摘要：

目的 通过UPLC-HRMS 检测分析体外人肝微粒体模型中合成大麻素类新精神活性物质AB-CHMINACA的代谢物并与一例真实滥用者的尿液样本进行对比，从而对体外人肝微粒体模型预测体内代谢物的一致性进行评价研究。方法 通过建立体外人肝微粒体孵育模型模拟人体体内代谢过程，尿液样本经简单的乙腈沉淀蛋白后利用高分辨质谱（HRMS）分析体内代谢物以确定代谢发生位点、代谢途径和体内尿液标志物。结果 AB-CHMINACA在人肝微粒体体外模型中共生成了10种代谢产物，其主要代谢途径为甲酰胺水解、甲基丙基侧链羟化、N-脱烷基和酰胺水解。其中，甲酰胺水解代谢物M1、甲基丙基侧链羟化代谢物M4和N-脱烷基合并甲酰胺水解代谢物M10在AB-CHMINACA滥用者的尿液样本中均有发现。结论 该体外代谢模型实验方法简便快捷，可在一定程度上预测AB-CHMINACA的体内代谢物。推荐AB-CHMINACA的甲酰胺水解代谢物和甲基丙基侧链羟化代谢物作为AB-CHMINACA滥用者尿液样本分析的生物标志物。

关键词:

AB-CHMINACA, 合成大麻素, 高分辨质谱, 肝微粒体