基于超高效液相色谱-四极杆飞行时间质谱技术的洋川芎内酯H在大鼠体内的代谢产物分析

刘明亮, 张奥, 段天华, 牛丽颖, 冯薇

中国药学杂志 ›› 2022, Vol. 57 ›› Issue (18) : 1549-1556.

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中国药学杂志 ›› 2022, Vol. 57 ›› Issue (18) : 1549-1556. DOI: 10.11669/cpj.2022.18.008
论著

基于超高效液相色谱-四极杆飞行时间质谱技术的洋川芎内酯H在大鼠体内的代谢产物分析

  • 刘明亮, 张奥, 段天华, 牛丽颖*, 冯薇*
作者信息 +

Metabolite Identification of Senkyunolide H in Rats by Ultra-High Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry

  • LIU Ming-liang, ZHANG Ao, DUAN Tian-hua, NIU Li-ying*, FENG Wei*
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摘要

目的 采用超高效液相色谱-四极杆飞行时间质谱(UHPLC-Q-TOF-MS)技术对洋川芎内酯 H 在大鼠体内的代谢产物进行分析鉴定。方法 SD大鼠灌胃给药后,收集其血浆、尿液、胆汁和粪便,并对样品进行前处理。采用ThermoAccucore C18色谱柱(2.1 mm×150 mm,2.6 μm),以体积分数0.1%乙酸-水(A相)-乙腈(B相)作为流动相进行梯度洗脱。根据准分子离子峰和碎片离子信息,结合对照品与文献报道,对大鼠血浆、尿液、胆汁和粪便中的原型成分及其代谢产物进行鉴定。结果 最终在大鼠血浆、尿液、胆汁和粪便中共检测到32个代谢产物,包括24个Ⅰ相和8个Ⅱ相代谢物。结论 洋川芎内酯 H 主要的体内代谢反应包括氧化、氢化、去羟基化、甲基化、葡萄糖醛酸化、硫酸酯化、半胱氨酸结合、谷氨酰胺结合以及相关的复合反应等。本研究应用高分辨液质联用技术阐明了洋川芎内酯 H 在大鼠体内的代谢产物,为今后药效学和药理学研究奠定了基础。

Abstract

OBJECTIVE To identify the metabolites of senkyunolide H in rats by Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS).CONCLUSION Plasma, urine, bile and feces samples of SD rats were collected and processed after oral administration of senkyunolide H. Chromatographic separation was performed on the Thermo Accucore C18(2.1 mm×150 mm, 2.6 μm) with the mobile phase of 0.1% acetic acid-water(phase A)-acetonitrile(phase B) for gradient elution. According to the information of accurate mass measurements and fragment ions, combined with the reference materials and literature reports,the prototype component and its metabolites in plasma, urine, bile and feces of rats were identified.RESULTS A total of 32 metabolites were detected in plasma, urine, bile and feces of rats, including 24 phase Ⅰ metabolites and 8 phase Ⅱ metabolites.CONCLUSION The major metabolic pathways of senkyunolide H in vivo includes oxidation, hydrogenation, dehydroxylation, methylation, glucuronide conjugation, sulfate conjugation, cysteine conjugation, glutamine conjugation and their composite reactions. In this paper, the metabolites of senkyunolide H in rats are rapidly elucidated by UHPLC-Q-TOF-MS, which lay a foundation for the study of pharmacology and pharmacodynamics in the future.

关键词

超高效液相色谱-四极杆飞行时间质谱 / 洋川芎内酯 H / 代谢产物 / 代谢途径

Key words

UHPLC-Q-TOF-MS / senkyunolide H / metabolite / metabolic pathway

引用本文

导出引用
刘明亮, 张奥, 段天华, 牛丽颖, 冯薇. 基于超高效液相色谱-四极杆飞行时间质谱技术的洋川芎内酯H在大鼠体内的代谢产物分析[J]. 中国药学杂志, 2022, 57(18): 1549-1556 https://doi.org/10.11669/cpj.2022.18.008
LIU Ming-liang, ZHANG Ao, DUAN Tian-hua, NIU Li-ying, FENG Wei. Metabolite Identification of Senkyunolide H in Rats by Ultra-High Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry[J]. Chinese Pharmaceutical Journal, 2022, 57(18): 1549-1556 https://doi.org/10.11669/cpj.2022.18.008
中图分类号: R969   

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基金

国家自然科学基金资助(82104358);河北省省级科技计划项目资助(20372502D,21372503D);河北省自然科学基金面上项目资助(H2021423066);河北中医学院科技能力提升项目资助(KTY2019063);河北中医学院大学生创新项目资助(202114432076,202114432171)
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