基于HPLC-Q-Exactive Orbitrap-MS技术的异绿原酸A体内代谢产物分析

Metabolite identification of isochlorogenic acid A in rats by HPLC-Q-Exactive Orbitrap-MS

异绿原酸A(ICA)为茵陈等多种中药的主要药效成分。该研究旨在鉴定口服给药ICA的大鼠血浆、尿液和粪便中的代谢产物,并推测其潜在的代谢途径。ICA灌胃大鼠后,收集不同时间点(段)的血浆、尿液和粪便样品,利用高效液相色谱-四极杆静电场轨道阱质谱(HPLC-Q-Exactive Orbitrap-MS)技术,结合对照品比对保留时间、裂解规律总结和文献数据,对生物样品中代谢产物进行结构鉴定。从大鼠样品中初步鉴定了ICA的39个代谢产物(M1~M39),其中31个来自于血浆(M1~M10、M12~M24、M26~M28、M30、M34~M35、M38~M39)、34个来自于尿液(M1~M11、M13~M15、M19~M25、M27~M39)、11个来自于粪便(M2~M3、M6、M15、M21~M23、M32、M34、M36~M37),主要代谢途径包括水解、葡萄糖醛酸化、甲基化和磺酸化反应等。该研究揭示了ICA在大鼠血浆、尿液和粪便中的代谢情况,对深入阐明其药理活性成分提供参考。

Isochlorogenic acid A(ICA)is the main active component of several TCMs,such as Artemisiae Scopariae Herba.This study aims to identify the metabolites of orally administered ICA in rat plasma,urine,and feces,and to speculate on its potential metabolic pathways.Rats were administered ICA orally,and samples of plasma,urine,and feces were collected at different time points.High-performance liquid chromatography-quadrupole Exactive Orbitrap-mass spectrometry(HPLC-Q-Exactive Orbitrap-MS)was used in combination with reference standards,retention time comparison,fragmentation pattern analysis,and literature data to identify the metabolites in the biological samples.A total of 39 metabolites(M1-M39)of ICA were preliminarily identified from rat samples,including 31 from plasma(M1-M10,M12-M24,M26-M28,M30,M34-M35,M38-M39),34 from urine(M1-M11,M13-M15,M19-M25,M27-M39),and 11 from feces(M2-M3,M6,M15,M21-M23,M32,M34,M36-M37).The main metabolic pathways included hydrolysis,glucuronidation,methylation,and sulfonation reactions.This study revealed the metabolic profile of ICA in rat plasma,urine,and feces,providing references for the in-depth elucidation of its pharmacologically active components.