LC-MS/MS研究人体及人肝微粒体内盐酸非洛普代谢产物  

Study on the Metabolites of Phenoprolamine Hydrochloride in Human Body and Human Liver Microsomes by LC-MS/MS

作　　者：黄琳[1] 张苑铃[1] 赵立波[1] 陈汇[2] 冯婉玉[1] 

机构地区：[1]北京大学人民医院药剂科,北京100044 [2]华中科技大学同济医学院,武汉430030

出　　处：《中国药学杂志》2012年第5期371-375,共5页Chinese Pharmaceutical Journal

摘　　要：目的通过在体及离体实验阐明盐酸非洛普代谢情况。方法健康志愿者口服盐酸非洛普60 mg,收集系列时间点血样,采用液相色谱串联质谱法检测志愿者血浆中的代谢产物并推测其可能结构;在建立人肝微粒体孵育体系中加入盐酸非洛普,常规温孵,采用液质联用仪分析孵育体系中的代谢产物,与在体实验进行对比。结果在志愿者血浆中,除原型外检测到1个代谢产物,代谢物的m/z为212.1,推测其结构可能为盐酸非洛普分子中间断裂产物;在人肝微粒体孵育体系中,除原型外共检测到6个代谢产物,m/z分别为360.1、342.2、415.1、281.4和330.2,推测其分别为盐酸非洛普氧化、脱氢、甲基化并结合甘氨酸、失掉相对分子质量62.6片段以及脱甲基的产物。结论盐酸非洛普在志愿者体内及体外人肝微粒体孵育体系中的主要代谢产物不同。盐酸非洛普在人体内可能存在肝脏以外的其他代谢途径,并起主要作用。OBJECTIVE To study the metabolites of phenoprolamine hydrochloride in human body and in human liver microsomes. METHODS Two volunteers were administrated with 60 mg of phenoprolamine hydrochloride, and plasma samples were collected in specified time points; phenoprolamine hydrochloride was incubated in human liver microsomes. All the metabolites were identified with the LC-MS/MS system. RESULT One key metabolite was detected in human plasma which m/z was 212.1. Six metabolites were detected in human liver microsomes and the m/z were separately 360.1, 342.2, 415.1, 281.4 and 330.2. Based on metabolite analysis, several metabolic pathways in human body and human liver microsomes were proposed. CONCLUSION The metabolites of phenoprolamine hydrochloride in human body were different with that in human liver microsomes. We assumed phenoprolamine hydrochloride would metabolize mainly through other pathway but not in the liver.

关 键 词：盐酸非洛普 液相色谱串联质谱法 人肝微粒体 肝外代谢途径 

分 类 号：R965[医药卫生—药理学]