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目的 研究苯丙哌林在人体内的羟基化代谢过程。方法 选择 10名健康男性受试者单剂量口服 6 0mg苯丙哌林 ,收集 0～ 2 4h尿样 ,经固相萃取后用LC/MSn 法检测羟基化代谢产物。利用微生物转化法和半制备HPLC获得其中两种代谢产物的对照品 ,并经NMR鉴定结构。根据质谱断裂规律进一步推测结合型代谢物的结构。结果在人尿中发现苯丙哌林的 5种羟基化代谢产物和它们与内源性葡糖醛酸和硫酸的结合物 ,与代谢物对照品的液相色谱和质谱信息比较 ,确证了其中两种代谢产物的结构分别为 4″ 羟基苯丙哌林和 4 羟基苯丙哌林。结论 苯丙哌林的羟基化代谢优先发生在芳环烷氧基对位 ,5种羟基化代谢产物在尿中主要以葡糖苷酸或硫酸酯结合物形式存在。
Objective To study the process of hydroxylated metabolism of benproperine in human. Methods Ten healthy male subjects were given single oral dose of 60 mg benproperine and urine samples were collected for 0 ~ 24 hours. The hydroxylated metabolites were detected by LC / MSn after solid phase extraction. The reference substance of the two metabolites was obtained by microbial transformation and semi-preparative HPLC, and the structure was confirmed by NMR. The structure of the bound metabolites is further speculated based on the rule of mass spectrum fragmentation. Results In human urine, five hydroxylated metabolites of benproperine and their conjugates with endogenous glucuronic acid and sulfuric acid were compared with the LC and MS information of the metabolite reference to confirm that The structures of the two metabolites were 4 "hydroxybenproperine and 4 hydroxybenproperine.CONCLUSION Hydroxylated metabolism of benproperine preferentially occurs at the para-position of arylcycloalkoxy, and the five hydroxylated metabolites at Urine mainly glucuronide or sulfate conjugate form.