高效液相色谱-串联质谱及特异性抑制剂探针方法研究异嗪皮啶的体外CYP450代谢产物及代谢亚型  

Studies on In Vitro Metabolites and Cytochrome P450 Isoforms Involved in Microsomal Metabolism of Isofraxidin by LC-MSn and Specific Inhibitor Probes

作　　者：毕云枫[1,2] 朱洪彬[2] 郑重[2] 刘志强[2] 宋凤瑞[2] 

机构地区：[1]吉林农业大学,食品科学与工程学院,长春130118 [2]中国科学院长春应用化学研究所,长春质谱中心,长春130022

出　　处：《分析化学》2013年第9期1391-1395,共5页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金(No.81073040)项目;国家博士后基金项目(No.2011M500625)资助

摘　　要：利用高效液相色谱-串联质谱及特异性抑制剂探针方法研究了异嗪皮啶在大鼠肝微粒体CYP450中的代谢产物及代谢亚型。结果表明,异嗪皮啶在大鼠肝微粒体的代谢时间为2 h最佳,其主要代谢产物有5种。CYP 3A,CYP 2C,CYP 2E1等亚型为异嗪皮啶在大鼠肝微粒体内的主要代谢酶。本方法为进一步研究药物-药物相互作用提供了依据。Isofraxidin（IF） is a coumarin compound that can be isolated from some medicinal plants,such as Acanthopanax senticosus,Sarcandra glabra etc.It has many bio-activities such as anti-fatigue,anti-bacterial,anti-tumour activity and immuno-accommondating action.In this study,LC-MSn method was developed for analyzing isofraxidin and its metabolites in rat liver microsomes.The results showed that the optimum incubations time for the isofraxidin in rat liver microsomal was 2 h.Five metabolites were found and characterized in rat liver microsomal incubations by LC-MSn analysis.Various specific inhibitors of cytochrome P450（CYP450） as probes were used to identify the isoforms of CYP450.Our research results suggested that isofraxidin metabolism by rat liver microsomes was significantly correlated with CYP 3A,CYP 2C and CYP 2E1 isoforms related activity.

关 键 词：异嗪皮啶 细胞色素P450 代谢 高效液相色谱-串联质谱 特异性抑制剂探针 

分 类 号：R284[医药卫生—中药学]