苯环喹溴铵在大鼠肝微粒体中的代谢转化研究

目的:建立检测大鼠肝微粒体中苯环喹溴铵代谢产物的方法,验证其在大鼠体内的代谢途径。方法:采用大鼠肝微粒体体外温孵法,建立液相色谱-质谱法测定并分析肝微粒体中苯环喹溴铵及其代谢物。色谱及质谱条件如下:色谱柱为TSK-gelODS-80Ts,流动相为甲醇-40mmol·L-1的乙酸铵水溶液(含0.1%甲酸)梯度洗脱;正离子模式,扫描型离子检测。结果:在体外代谢系统中,根据质谱碎片信息检测出6个代谢产物,分别是苯环喹溴铵的二羟基、单羟基和氧化产物。结论:建立的液相色谱-质谱法能够准确灵敏地测定大鼠肝微粒体中苯环喹溴铵的代谢产物,验证了在大鼠体内苯环喹溴铵的代谢部位在环戊烷基上。

Metabolism of Bencycloquidium Bromide in Rat Liver Microsome

OBJECTIVE：To establish the determination method of metabolic products of bencycloquidium bromide（BCQB） in rat liver microsome and to verify the metabolic pathway of it in vivo.METHODS：Incubation system of rat liver microsome was adopted,and BCQB and its metabolites in rat liver microsome were detected by LC-MS/MS.The determination condition was as follows：TSK-gel ODS-80 Ts column,mobile phase of methanol-40 mmol·L^-1 ammonium acetate buffer solution（0.1% formic aicd,gradient elution）.The standard positive ion mode was selected under the full scan.RESULTS：6 metabolites of BCQB were detected in liver microsome incubation system according to MS fragment information,which were di-hydroxyl cyclopentyl BCQB,mono-hydroxyl BCQB and mono-oxide BCQB.CONCLUSION：The metabolites of BCQB in liver microsome can be accurately detected by HPLC-MS/MS.This research has further confirmed cyclepentane is the metabolic site of BCQB in vivo in rats.