喜树碱衍生物NCP4在不同种属肝微粒体中代谢稳定性研究  

Metabolism of camptothecin derivative NCP4 in liver microsomes among different species in vitro

作　　者：刘琼艳 张美琴 卿晨 李霁 LIU Qiong-yan;ZHANG Mei-qin;QING Chen;LI Ji(School of Pharmaceutical Science&Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming 650500,China;Yunnan Xinxing College of Professional Technology,Kunming 650501,China)

机构地区：[1]昆明医科大学药学院暨云南省天然药物药理重点实验室,昆明650500 [2]云南新兴职业学院,昆明650501

出　　处：《天然产物研究与开发》2019年第11期1968-1974,共7页Natural Product Research and Development

基　　金：科技部重大新药创制专项(2011ZX09401026);国家自然科学基金-地区基金(81960652);云南省科技厅-昆明医科大学应用基础研究联合专项-青年博士项目(201801YH00036)

摘　　要：探讨喜树碱衍生物NCP4在人、SD大鼠、beagle犬肝微粒体中的体外代谢稳定性及代谢产物。应用体外肝微粒体孵育体系,采用HPLC-UV-MS(Q-TOF)法,考察NCP4的代谢稳定性,并推断其代谢产物结构。结果显示,NCP4在Beagle犬和人肝微粒体温孵代谢动力学参数T l/2(min)相当,而在SD大鼠肝微粒体温孵的T l/2(min)相差较大;此外,NCP4在SD大鼠肝微粒体中生成m/z[M+Na]^+为502、460、344的代谢产物,在Beagle犬、人肝微粒体中生成m/z[M+Na]^+为388、390、448的代谢产物。结果表明Beagle犬与人肝微粒体温孵体系中NCP4底物的代谢稳定性基本一致,且NCP4在beagle犬与人的肝微粒体代谢产物相同。可以为NCP4临床前安全性评价的实验动物选择提供依据。The metabolic stability and metabolites of NCP4 incubated with human,SD rat and dog liver microsomes in vitro were studied.NCP4 and its metabolites were separated and tested by HPLC-UV-MS(Q-TOF).The results showed that T l/2(min)of NCP4 obtained from dog and human liver microsomes were comparable;In addition,4 metabolites generated from NCP4 in rat liver microsome were found,and another 3 metabolites generated from NCP4 in human and dog liver microsomes were detected.All results mentioned above indicated that the metabolites of NCP4 in liver microsome from dogs were consistent with that from human.The results can be used to select 1aboratory animals for safety evaluation of NCP4 in preclinical study.

关 键 词：NCP4 喜树碱衍生物 肝微粒体 代谢产物 代谢稳定性 

分 类 号：R284.1[医药卫生—中药学] R917[医药卫生—中医学]