PAC-1在人肝微粒体中的代谢产物分析

Identification of procaspase activating compound 1 metabolites in human liver microsomes

目的初步阐明procaspase activating compound 1(PAC-1)在人肝微粒中的代谢情况。方法在一定的人肝微粒体浓度中加入药物,温孵后,采用液相色谱-飞行时间质谱法对孵化体系中的代谢产物进行分析。在正离子模式下,采用全扫描方式对代谢物进行检测。结果在人肝微粒体孵化体系中,除原型外共检测到4个代谢产物,代谢物的结构为脱苄基PAC-1和羟基化PAC-1。结论PAC-1在人肝微粒体系中的代谢途径为脱苄基化和羟基化。本研究结果对于进一步了解PAC-1在人体中的代谢和结构修饰具有重要的意义。

Objective To elucidate the metabolic pathway of procaspase activating compound 1（PAC-1）in human liver microsomes.Methods In this study,a liquid chromatography-time of flight mass spectrometric method was developed and applied to characterize the metabolites of PAC-1 after incubation with human liver microsomes.The analysis was performed under positive ion model with full scan method.Results Besides PAC-1,four metabolites were detected and the structures were proposed.Based on metabolite analysis,several PAC-1 metabolic pathways in human liver microsomes were proposed.Conclusions The result provides important information for the drug metabolism and structural modification research of PAC-1.