液相色谱-串联电喷雾离子阱质谱法研究人尿中埃坡霉素D的主要代谢产物  

Study on essential metabolites of Epothilone D in human urine by liquid chromatography-mass spectrometry

作　　者：张春玲[1,2] 朱晓霞[1] 齐文渊[1] 刘江林[1,2] 孟志云[1] 顾若兰[1] 王延琳[1] 吴卓娜[1] 孙国祥[2] 窦桂芳[1] 

机构地区：[1]军事医学科学院野战输血研究所,北京100850 [2]沈阳药科大学

出　　处：《中国临床药理学与治疗学》2009年第3期307-312,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国际科技合作重点项目计划(2005DFA30080)

摘　　要：目的:研究埃坡霉素D在人尿中的主要代谢产物。方法:受试者6名静脉滴注埃坡霉素D,收集0～72h尿样,经SPE固相萃取小柱分离纯化后,采用液相色谱-串联电喷雾离子阱质谱法(LC-MSn)对样品进行分析,通过比较空白尿样和给药后的尿样的总离子流色谱图和选择离子扫描色谱图,分析可能的代谢产物。代谢产物的结构鉴定主要依据代谢产物的各级质谱图与原药的各级质谱图的相关性推断所得。结果:在人尿中共检测到11种主要的代谢产物,根据所提供的代谢产物标准品鉴定出3种代谢产物的结构,代谢方式主要有氧化、还原、水解和结合反应。结论:本方法选择性好,为深入研究埃坡霉素类药物在人体内的代谢规律提供了可靠的方法和可参考的依据。AIM： To investigate the essential metabolites of Epothilone D in human urine. METH- ODS： The urine samples of s/x volunteers after intervenous drop infusion of 125 mg/m2 were collected within 0 - 72 h, the samples were purified and separated through Cls solid-phase extraction column and analyzed with liquid chromatography-mass spectrometry. The potential metabolites were analyzed through comparing the TIC and SIM chromatograms of the blank urine and sample urine, and the structure of the metabolites were identified through the correlation of the full scan MS^n spectra of Epothilone D and the metabolites. RESULTS： Eleven metabolites were found in human urine. There were three kinds of structure of metabo- lites, the metabolic ways of oxidation, hydrogenise, hydrolization and association reaction. CONCLUSION： The method was proved sensitively and selectively, and it is possible to supply a reliable reference for further study on the metabolites of Epothilones.

关 键 词：高效液相色谱-串联质谱 埃坡霉素D SPE C18固相萃取技术 代谢产物分析 

分 类 号：R969.1[医药卫生—药理学]