采用LC-HRMS分析米氮平在人肝微粒体中的体外代谢产物  

Analysis of In Vitro Mirtazapine Metabolites in Human Liver Microsomes by LCHRMS

作　　者：张瑛 张文芳 徐多麒 覃仕扬 杨士云 乔静 ZHANG Ying;ZHANG Wen-fang;XU Duo-qi;QIN Shi-yang;YANG Shi-yun;QIAO Jing(Key Laboratory of Forensic Toxicology,Ministry of Public Security,Forensic Science Service of Beijing Public Security Bureau,Beijing 100192,China;Shanghai Key Laboratory of Forensic Medicine,Key Laboratory of Forensic Science,Ministry of Justice,Shanghai Forensic Service Platform,Academy of Foren-sic Science,Shanghai 200063,China)

机构地区：[1]北京市公安司法鉴定中心法庭毒物分析公安部重点实验室,北京100192 [2]司法鉴定科学研究院、上海市法医学重点实验室、司法部司法鉴定重点实验室、上海市司法鉴定专业技术服务平台,上海200063

出　　处：《法医学杂志》2024年第6期569-574,共6页Journal of Forensic Medicine

摘　　要：目的建立并优化人肝微粒体体外温孵体系,研究米氮平的体外代谢产物及其可能的代谢途径。方法选择米氮平的3种主要代谢产物进行肝微粒体温孵条件优化,采用液相色谱-高分辨质谱联用仪进行分析,鉴定米氮平的体外代谢产物和代谢途径。结果在体外肝微粒体温孵实验中发现并鉴定了10个代谢产物,包括9个Ⅰ相代谢产物和1个Ⅱ相代谢产物,其中包含5个新的代谢产物,1条新的代谢途径。参与Ⅰ相代谢的途径包括氮去甲基化、羟基化、氧化、还原等,Ⅱ相生物转化代谢产物主要由葡萄糖醛酸化反应产生。结论本研究建立的肝微粒体体外温孵体系中发现的代谢产物与文献报道的米氮平主要代谢产物一致,均为N-去甲米氮平、8-羟基米氮平和米氮平氮氧化物,研究结果可为米氮平案件的确认提供依据,也为其他物质代谢产物的研究提供了参考。Objective To establish and optimize an in vitro incubation system with human liver microsomes and investigate the in vitro metabolites and possible metabolic pathways of mirtazapine.Methods Three major metabolites of mirtazapine were selected to optimize the incubation conditions of liver microsomes.The metabolites of mirtazapine were analyzed by liquid chromatography-high resolution mass spectrometry(LC-HRMS)to identify the in vitro metabolites and metabolic pathways of mirtazapine.Results Ten metabolites,including nine phaseⅠmetabolites and one phaseⅡmetabolite,were identified in the in vitro liver microsome incubation.Among them,five new metabolites and one new metabolic pathway were discovered.The pathways involved in phaseⅠmetabolic included methylation,hydroxylation,oxidation,reduction,etc.,while the phaseⅡbiotransformation was mainly glucuronidation.Conclusion The metabolites discovered in this study are consistent with the main metabolites of mirtazapine reported in literature,which are N-desmethylmetazapine,8-hydroxy mirtazapine and mirtazapine-N-oxide.The results can provide basis for the confirmation of mirtazapine cases and provide reference for the study of other substances.

关 键 词：法医学 毒物分析 米氮平 人肝微粒体 代谢产物 代谢途径 液相色谱-高分辨质谱法(LC-HRMS) 

分 类 号：R89[医药卫生—法医学] DF795.1[医药卫生—临床医学] D919.1[政治法律—诉讼法学]