基于UPLC-Q-TOF-MS的林泽兰内酯C血清药物化学研究

目的:采用超高效液相色谱四级杆飞行时间质谱仪联用技术(UPLC-Q-TOF-MS)分析鉴定大鼠灌胃林泽兰内酯C后血清中的代谢产物,阐明林泽兰内酯C代谢转化过程。方法:灌胃给药后眼眶取血,制备血清样品,采用Agilent ZORBAX XDB-C8柱,流动相为乙腈-0.2%甲酸水,梯度洗脱,动态背景扣除触发信息关联采集进行MS/MS数据采集。结果:结合PeakView、MetabolitePilot代谢物鉴定软件,分析结果显示林泽兰内酯C经过水解、氧化、还原、甲基化等Ⅰ相反应及葡萄糖醛酸化、磷酸化、谷胱甘肽结合等Ⅱ相反应,形成系列相关代谢产物共26种。结论:该方法高效灵敏,明确了林泽兰内酯C在大鼠体内的代谢转化过程,为中药野马追的药效物质基础、新药研发及临床应用研究等提供相关科学参考。

Serum medicinal chemistry study of Eupalinilide C based on UPLC-Q-TOF-MS

Objective:To study the metabolites in rats’serum after the administration of Eupalinilide C by ultraperformance liquid chromatography-quadrupole-time of flight mass spectrometry to clarify the metabolic transformation process of Eupalinilide C.Method:Blood samples were taking from the eyelids after intragastric administration to prepare serum samples.Agilent ZORBAX SB-C8(2.1 mm×100 mm,1.8μm)column was used,the mobile phase was acetonitrile-0.2%formic acid aqueous solution,gradient elution,dynamic background subtraction(DBS)technology was employed to trigger information dependent acquisition(IDA)to obtain the characteristic fragment ions of metabolites.Results:Metabolite analysis and identification was done by combining PeakView and MetabolitePilot.Analysis result showed that the Eupalinilide C was subjected to phase I reaction such as hydrolysis,oxidation and reduction,and phase I reaction such as glucuronidation and glutathione binding to form a series of 26 related metabolites.Conclusion:This method is sensitive and efficient,and the metabolic transformation process of Eupalinilide C in rats is clarified.It provides a scientific reference for the pharmacodynamic substance basis,new drug development and clinical application of Eupatorium lindleyanum.