右旋和左旋黄皮酰胺在大鼠体内代谢转化的研究

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，并有明显的立体选择性。

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

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.