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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。
Objective: To study the main metabolites of epothilone D in human urine. Methods: Six patients were injected with epothilone D intravenously. Urine samples were collected for 0-72h and purified by SPE solid-phase extraction cartridge. Liquid chromatography-tandem electrospray ion trap mass spectrometry (LC-MSn ) The samples were analyzed and probable metabolites analyzed by comparing the total ion chromatogram of the blank and administered urine samples with the selected ion scan chromatogram. Structural identification of metabolites is mainly based on the metabolites at all levels of mass spectrometry and the original mass spectra at all levels inferred from. Results: A total of 11 major metabolites were detected in human urine. The structures of the three metabolites were identified according to the metabolite standards provided. The main metabolic processes were oxidation, reduction, hydrolysis and conjugation. Conclusion: The method has good selectivity and provides a reliable method and a reference basis for further study of metabolism of epothilones in human.