[关键词]
[摘要]
目的 分析大鼠灌胃给予异绿原酸C(4,5-二咖啡酰奎宁酸)后粪便、尿液及血浆内存在的代谢产物并推测其在大鼠体内的代谢途径。方法 大鼠按20 mg·kg-1一次性灌胃给予异绿原酸C后,收集不同时间(段)的粪便、尿液及血浆,采用超高效液相色谱与Q-Exactive Plus Orbitrap 高分辨质谱技术(UPLC-Q-Exactive Plus Orbitrap MS)+质谱自带的软件联合的方法分析,对生物样品进行检测,并完成鉴定其代谢产物。结果 基于总离子流色谱图和一级二级质谱提供的分子离子和碎片离子等精确信息,最终从大鼠粪便、尿液和血浆中共发现11种成分,包括1个原型和10个代谢产物,涉及的代谢途径有水解、甲基化、氧化、还原、葡萄糖醛酸化、硫酸酯化等。结论 本实验建立的分析方法检测快速、结果准确、灵敏度高,符合生物基质样品分析相关要求,适用于大鼠粪便、尿液和血浆中异绿原酸C代谢产物的分析,为异绿原酸C的药效作用机制及药动学研究提供一定参考价值。
[Key word]
[Abstract]
Objective To identify the metabolites in rat feces, urine and plasma after oral administration of isochlorogenic acid C (4,5-dicaffeoylquinic acid) and to further propose its metabolic pathway in vivo.Methods Wistar rats were administered with isochlorogenic acid C by oral administration at a dose of 20 mg·kg-1. The feces, urine and plasma were harvested at different time points, and the samples were analyzed by an ultra-high performance liquid chromatography combined with Q-Exactive Plus Orbitrap mass spectrometer (UPLC-Q-Exactive Plus Orbitrap MS) and its software to identify the metabolites.Results According to the accurate information provided by total ion chromatography, mass spectrometry (MS) and MS/MS data, a total of 11 components in rat feces, urine and plasma including prototype and 10 metabolites were observed. And the metabolic pathway included hydrolysis, methylation, oxidation, reduction, glucuronidation, sulfation and so on.Conclusion The analytical method established in this experiment has the advantages of rapid detection, accurate results and high sensitivity. It meets the relevant requirements of biological matrix sample analysis. It is suitable for the analysis of isochlorogenic acid C metabolites in rat feces, urine and plasma, and provides a certain reference for the pharmacodynamic mechanism and pharmacokinetics of isochlorogenic acid C.
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[基金项目]
山东省自然科学基金委员会面上项目(ZR2019MH051):基于入血活性成分追踪和代谢组学研究中药桑白皮抗高血压的药效物质基础及作用机制,负责人:邓志鹏。