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

周海燕 孟志云 窦桂芳 马金兰 楼雅卿 章国良

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

周海燕孟志云窦桂芳马金兰楼雅卿章国良

LC-MSⁿanalysis of metabolites of 1, 2-bis (1, 2-benzisoselenazolone- 3(2H)-ketone)-ethane, a novel anti-cancer agent in rat

ZHOU Hai-Yan

摘要

摘要:
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200 mg·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。

Abstract:
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.

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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-MSn analysis of metabolites of 1, 2-bis (1, 2-benzisoselenazolone- 3(2H)-ketone)-ethane, a novel anti-cancer agent in rat

LC-MSⁿanalysis of metabolites of 1, 2-bis (1, 2-benzisoselenazolone- 3(2H)-ketone)-ethane, a novel anti-cancer agent in rat