UHPLC-MS/MS研究抗肿瘤化合物E28在不同种属肝微粒体中的代谢产物  

Metabolites identification of anti-tumor compound E28 in liver microsomes from different species by UHPLC-MS/MS

作　　者：谭艳 汤明海[2] 杜蕾蕾[1] 万丽[1] TAN Yan;TANG Ming-hai;DU Lei-lei;WAN Li(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu611137,China;State Key Laboratory of Biotherapy,West China Hospital of Sichuan University,Chengdu610041,China)

机构地区：[1]成都中医药大学药学院,成都611137 [2]四川大学华西医院生物治疗国家重点实验室,成都610041

出　　处：《中国新药杂志》2022年第20期2044-2050,共7页Chinese Journal of New Drugs

基　　金：四川省应用基础研究发展计划资助项目(2020YJ0375);四川省重点研发计划资助项目(2021YFS0042)。

摘　　要：目的:应用肝微粒体体外孵育体系,研究化合物E28在人、SD大鼠、小鼠、恒河猴和比格犬的肝微粒体中的代谢产物和代谢途径,为体内代谢动物的选择提供依据。方法:运用UHPLC-MS/MS技术,联合Compound Discoverer TM 3.0软件,根据代谢产物与母体药物相似的裂解方式,鉴定代谢产物的化学结构。结果:在体外肝微粒体中,检测到E28的代谢产物共18个。在人、SD大鼠、小鼠、恒河猴和比格犬的肝微粒体中,代谢产物分别有9,11,10,13和15个;代谢途径以氧化、水合为主。结论:E28在体外肝微粒体中的代谢产物无明显种属差异,在小鼠肝微粒体中的代谢产物与人肝微粒体基本一致,提示可以选择小鼠作为进一步药代和毒代研究的动物模型。Objective: To study the metabolites and metabolic pathways of E28 in liver microsomes of human, SD rat, mouse, rhesus monkey and beagle, in order to provide a basis for the selection of metabolic animals in vivo. Methods: The metabolites were analyzed by UHPLC-MS/MS, and their chemical structures were identified with Compound Discoverer TM 3.0 software through comparing the cleavage mode to that of the parent compound. Results: A total of 18 E28 metabolites were detected in liver microsomes in vitro. The number of metabolites identified in liver microsomes of human, SD rat, mouse, rhesus monkey and beagle were 9, 11, 10, 13 and 15, respectively. The implicated main metabolic pathways include oxidation and hydration. Conclusion: There is no obvious species differences for metabolites of E28 in liver microsomes in vitro, and the metabolites in mouse liver microsomes are basically the same as those in human liver microsomes, suggesting that mice can be selected as an ideal animal model for further pharmacokinetic and toxicological studies.

关 键 词：E28 肝微粒体 代谢产物 UHPLC-MS/MS 

分 类 号：R965.1[医药卫生—药理学]