一叶萩碱的高效毛细管电泳手性分离及其大鼠体内立体选择性代谢研究  

STUDY ON THE CHIRAL SEPARATION OF SECURININE BY HIGH-PERFORMANCE CAPILLARY ELECTROPHORESIS AND ITS STEREOSELECTIVE METABOLISM IN RAT

作　　者：李晓海[1] 张金兰[1] 周同惠[1] 

机构地区：[1]中国医学科学院,中国协和医科大学药物研究所,北京100050

出　　处：《药学学报》2002年第1期50-53,共4页Acta Pharmaceutica Sinica

摘　　要：目的　建立一叶碱 (SE)的高效毛细管电泳手性分离方法。方法　以羟丙基 β 环糊精 (HP β CD)为手性选择剂 ,测定条件为 :分离介质 3 2mmol·L- 1 HP β CD的Tris H3PO4 缓冲液 ( 4 0mmol·L- 1 ,H3PO4 调至pH 6 0 ) ;分离电压 15kV ,柱温 16℃ ,压力进样 6s ,检测波长 2 5 4nm ;大鼠各生物样品碱化后乙酸乙酯萃取。结果　测定条件下SE基本达到基线分离 ,大鼠生物样品测定不受内源及代谢物干扰。大鼠ipSE经胆汁、尿和粪排泄以d型为主 ,具有立体选择性。结论　本法简便可靠 ,可适用于SE在大鼠体内立体选择性代谢研究。AIM To establish a high performance capillary electrophoresis (HPCE) chiral separation method for d securinine and l securinine, and use this method to investigate the stereoselective metabolism process of d and l securinine in Wistar rats. METHODS The electrophoretic condition and parameters were investigated and the optimized conditions were as following: the electrophoretic medium was 40 mmol·L -1 Tris H 3PO 4 buffer (pH adjusted to 6 0 with H 3PO 4) containing 32 mmol·L -1 HP β CD as chiral selector. Determination was carried out with a UV detector at 254 nm. The separations were performed at 16℃ with a positive voltage of 15 kV. Samples were injected into the capillary by pressure for 6 s. The biological samples (urine, bile, plasma and feces) of rats were alkalized and extracted with ethyl acetate. RESULTS The experimental results showed that the concentration of HP β CD, the concentration of the running buffer and the pH value of the buffer were the main important factors which effected the resolution. d Securinine and l securinine were separated at baseline level under the determination conditions. The determination was not interfered by endogenous components and metabolites. After ip administration, the rats excreted more d securinine than l securinine through bile, urine and feces. The metabolism process in rats was stereoselective. CONCLUSION This method is simple, reliable and suitable for studying the stereoselective metabolism of securinine in rats.

关 键 词：手性药物 一叶Qiu碱 高效毛细管电泳 手性分离 立体选择性代谢 

分 类 号：R914.5[医药卫生—药物化学]