右旋和左旋黄皮酰胺在大鼠体内代谢转化的研究  

BIOTRANSFORMATION OF (+)-AND (-)-CLAUSENAMIDE IN RATS

作　　者：姚庆强[1,3] 王琰[1] 杨树民 王慕邹[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 [2]中国兴奋剂检测中心,北京100029 [3]山东省医学科学院药物研究所

出　　处：《药学学报》2001年第3期224-228,共5页Acta Pharmaceutica Sinica

摘　　要：目的　研究黄皮酰胺在大鼠体内的代谢转化途径。方法　收集ip给药后大鼠的尿液、粪便及血液进行分析 ,寻找已知的代谢产物并通过HPLC DAD和HPLC MS分析寻找未知的代谢产物 ,确定大鼠体内的主要代谢途径。并通过比较 (+ ) ,(- ) 黄皮酰胺代谢的差异 ,初步研究其代谢转化的立体选择性。结果　HPLC分析发现 ,大鼠肝微粒体中所分离得到的 6个主要代谢产物均在体内存在 ,(+ ) ,(- ) 黄皮酰胺的代谢有明显的差异 ,根据MS碎片信息确定了一个新的代谢产物的结构 ,即N 去甲黄皮酰胺。结论　手性黄皮酰胺主要在肝脏中发生羟基化代谢反应 。AIM To study the metabolic pathway of chiral clausenamide in the rat and understand its stereoselectivity. METHODS The urine, feces and blood of rat were gathered after the drug was administered, the known metabolites were analyzed by HPLC DAD and one unknown metabolite was elucidated by using LC MS analysis. Metabolic stereoselectivity was determined by comparing the metabolic results of (+) and (-) clausenamide. RESULTS Six known metabolites were determined and one unknown metabolite was elucidated as N demethylclausenamide. The metabolic stereoselectivity was shown distinctly. CONCLUSION Chiral clausenamide was mainly metabolized by hydroxylation in liver and the biotransformation exhibited pronounced substrate stereoselectivity.

关 键 词：黄皮酰胺 体内代谢转化 立体选择性 高效液相色谱-质谱法 

分 类 号：R917[医药卫生—药物分析学] R969.1[医药卫生—药学]