乌头碱在豚鼠和小鼠肝微粒体细胞色素氧化酶中的代谢作用研究

摘要

OBJECTIVE: To study the difference of the metabolites of aconitine (AC) in liver microsornes of guinea pig and mice. METHODS: HPLC-HRMS and UPLC-MS/MS were developed to determine the metabolites of AC in two liver microsomes, after optimizing the cytochfome P450 reaction systems of AC in two liver microsomes. RESULTS: Eight metabolites were detected in both two reaction systems, and six of them was determined as CYP-mediated metabolites. The metabolic pathways were demethyl-ation, de-ethylation, dehydrogenation and oxidation reaction. CONCLUSION: There was no species different in the metabolic pathways of AC in liver microsomes of guinea pig and mice.%目的:研究乌头碱(AC)在豚鼠和小鼠体外肝微粒体中代谢产物的差异.方法:优化2个种属肝微粒体与AC的P450反应体系,应用高效液相色谱-高分辨质谱联用(HPLC-HRMS)和超高相液相色谱-多级质谱(UPLC-MS/MS)法测定AC在2种肝微粒体中的细胞色素氧化酶(CYP)代谢产物.结果:AC在2种肝微粒体中均代谢产生8种代谢产物,其中6种为CYP代谢产物；脱甲基、脱乙基、脱氢和氧化反应是其主要代谢特征.结论:乌头碱在豚鼠和小鼠体外肝微粒体中的CYP主要代谢途径相同.