小分子抗肿瘤化合物SPH0396在不同种属体内外代谢的比较  

Comparison of in vitro & in vivo metabolites of an anti-cancer small molecule SPH0396 in different species

作　　者：向志雄[1] XIANG Zhixiong(Central Research Institute, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, China)

机构地区：[1]上海医药集团股份有限公司中央研究院,上海201203

出　　处：《上海医药》2017年第21期70-75,共6页Shanghai Medical & Pharmaceutical Journal

摘　　要：目的 :比较研究SPH0396在不同种属的体内外代谢产物。方法 :采用超高效液相色谱-四极杆飞行时间质谱法(UPLC/Q-TOF MS),比较研究不同种属肝微粒体中SPH0396的体外代谢产物,并进一步研究比格犬和食蟹猴分别灌胃给予SPH0396后血浆中的代谢产物。结果 :SPH0396在体内外的代谢产物主要有N-去甲基代谢产物和氮氧化代谢产物。结论 :SPH0396在猴的体内外代谢产物与人肝微粒体基本一致,该研究结果可为临床前药代和安全性评价的实验动物选择提供依据。Objective：To compare in vitro in vivo metabolites of SPH0396 in different species.Methods：An ultrahigh performance liquid chromatography/quadruple time-of-flight mass spectrometry（UPLC/Q-TOF MS） method was applied to identify the metabolites in vitro and in plasma after oral administration of 10 mg/kg SPH0396 to beagle dogs and cynomolgus monkeys.Results：The main metabolites of SPH0396 in vitro in vivo were demethyl metabolites and N-oxidation metabolites.Conclusion：The main metabolites of SPH0396 in cynomolgus monkey are basically consistent with those in human liver microsomes.This result can provide basis for the selection of 1 aboratory animals in preclinical evaluation of pharmacokinetics and safety of SPH0396.

关 键 词：代谢产物 SPH0396 肝微粒体 UPLC/Q-TOF MS 不同种属 

分 类 号：R96[医药卫生—药理学]