液相色谱-串联质谱法分析抗肿瘤新药乙烷硒啉在大鼠体内的代谢产物

LC-MS^n analysis of metabolites of 1,2-[bis (1,2-benzisoselenazolone- 3(2H)-ketone)]-ethane,a novel anti-cancer agent in rat

本研究对抗肿瘤新药1,2-[二(1,2-苯并异硒唑-3(2H)-酮)]乙烷(乙烷硒啉,BBSKE)在大鼠体内的代谢产物进行鉴定。在灌胃给予大鼠单剂量乙烷硒啉200mg·kg-1后,采用液相色谱-串联质谱法(LC-MSn)对大鼠尿液、粪样、胆汁和血浆中的代谢产物进行检测,通过全扫描和选择离子扫描,以及根据多级质谱裂解规律对代谢物的结构进行分析。研究发现在大鼠尿样、粪样、胆汁和血浆中检测到3种Ⅰ相代谢产物和1种Ⅱ相代谢产物,其代谢途径分别为氧化、甲基化、硫甲基化和葡萄糖醛酸化反应,提示乙烷硒啉在大鼠体内的代谢方式可能是通过氧化、甲基化及葡萄糖醛酸化反应形成代谢产物。

This study is to elucidate the metabolic pathway of 1,2-[bis （1,2-benzisoselenazolone-3 （2H）-ketone）]-ethane （BBSKE） in rats.Rats were administrated with a single dose of BBSKE 200 mg·kg^-1.The metabolites in rat urine,feces,bile and plasma were identified by LC-MSn analysis.The characterization of fragment ions from LC-MSn chromatography and mass spectrometry was applied to the investigation of structures of metabolites.Three phase I metabolites were detected in rat urine and feces.Two of them were also found in plasma and one existed in bile.These products were derived from oxidized,methylated and S-methylated BBSKE,separately.One phase II glucuronide of BBSKE was also found in bile.Therefore,it is possible that BBSKE was metabolized by oxidization,methylation and glucuronidation.