吖啶酮衍生物H64在5种种属肝微粒体中的代谢产物分析  

Analysis of metabolite of acridone derivative H64 in liver microsomes from five species

作　　者：王欢[1] 汤明海[2] 万丽[1] WANG Huan;TANG Ming-hai;WAN Li(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan;State Key Laboratory of Biotherapy,West China Hospital of Sichuan University,Chengdu 610041,Sichuan)

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

出　　处：《中药与临床》2022年第5期43-47,共5页Pharmacy and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(81803705)。

摘　　要：目的:应用肝微粒体体外孵育体系,对吖啶酮衍生物H64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进行鉴定,并提出H64的主要体外代谢途径。方法:生物样品经过前处理,乙腈和0.1%甲酸水溶液为流动相,通过UHPLC-Q-Exactive Plus液质进行分析,使用Xcalibur 4.2以及Compound Discoverer^(TM)2.0软件对数据进行处理,及后期的人工筛选,鉴定H64在5种种属肝微粒体中可能的代谢产物。结果:共检测到11个代谢产物,其中9个为Ⅰ相代谢产物,包括氧化以及脱氧还原的代谢物;其余2个为Ⅱ相代谢产物,包括甲基化、乙酰化的代谢物。在人、SD大鼠、小鼠、恒河猴和比格犬的肝微粒体中分别检测出了9、6、7、7、7种代谢产物。结论:H64在各种属肝微粒体中,最主要的代谢途径为氧化。本研究能反映H64的体内代谢产物的大致情况。小鼠和人肝微粒体中的代谢产物种类最为接近,为H64早期代谢研究的实验动物的选择上提供了参考。Objective:Using the in vitro incubation system of liver microsomes,to identify the metabolites of acridone derivative H64 in the liver microsomes from human,SD rat,mouse,rhesus monkey and beagle dog,and propose the main in vitro metabolic pathways of H64.Method:The biological samples were pre-treated,and were analyzed by UHPLC-Q-Exactive Plus liquid and mass spectrometers using acetonitrile and 0.1%formic acid aqueous solution as mobile phases.Xcalibur 4.2 and Compound Discoverer^(TM)2.0 software was used for data processing and later manual screening,and to identify possible metabolites of H64 in the liver microsomes from the five species.Result:A total of 11 metabolites were detected,of which 9 were phaseⅠmetabolites,including oxidative and deoxy-reductive metabolites.The remaining 2 were phaseⅡmetabolites,including methylated and acetylated metabolites.9,6,7,7,and 7 metabolites were detected in the liver microsomes from human,SD rat,mouse,rhesus monkey and beagle dog,respectively.Conclusion:The main metabolic pathway of H64 is oxidation in the liver microsomes of various species.This study can reflect the general situation of the metabolites of H64 in vivo.The types of metabolites in mouse and human liver microsomes are the most similar,which provides a reference for the selection of experimental animals for the early metabolism study of H64.

关 键 词：吖啶酮衍生物 肝微粒体 代谢产物 代谢途径 

分 类 号：R285.5[医药卫生—中药学]