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引用本文:王红,崔议方,徐静,李亚男,林永强,李启艳,张加余.异欧前胡素在大鼠体内代谢产物的UHPLC-HRMS鉴定分析[J].中国现代应用药学,2023,40(19):2677-2686.
WANG Hong,CUI Yifang,XU Jing,LI Yanan,LIN Yongqiang,LI Qiyan,ZHANG Jiayu.UHPLC-HRMS Identification and Analysis of the Metabolites in Vivo of Isoimperatorin in Rats[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(19):2677-2686.
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异欧前胡素在大鼠体内代谢产物的UHPLC-HRMS鉴定分析
王红1,2, 崔议方2, 徐静2, 李亚男2, 林永强3, 李启艳3, 张加余1
1.滨州医学院药学院, 山东 滨州 264003;2.山东中医药大学药学院, 济南 250300;3.山东省食品药品检验研究院, 济南 250101
摘要:
目的 分析鉴定异欧前胡素在正常大鼠体内的代谢产物。方法 大鼠灌胃给药后,收集正常组和给药组大鼠的血浆、尿液和粪便样本,并以固相萃取柱提纯生物样品。采用UHPLC-HRMS(Q-Exactive Orbitrap MS)高分辨质谱对生物样品进行分析,并对代谢产物筛选鉴定。结果 在正、负离子模式下,根据所获得的精确分子质量、色谱保留行为、质谱裂解规律、特征碎片离子、对照品比对以及文献报道,最终分析鉴定了32个代谢产物。其代谢途径主要包括呋喃环开环、内酯水解、氧化、甲基化、葡萄糖醛酸化、硫酸酯化以及它们的复合反应。其中,葡萄糖醛酸化产物为首次发现。结论 本研究较为全面地阐明了异欧前胡素在正常大鼠体内的代谢转化情况,可为其进一步的药效学研究提供依据,并为呋喃香豆素类物质的代谢产物分析提供借鉴。
关键词:  异欧前胡素  体内代谢  UHPLC-HRMS(Q-Exactive Orbitrap MS)  代谢产物
DOI:10.13748/j.cnki.issn1007-7693.20222326
分类号:R969.1
基金项目:山东省泰山学者青年专家项目(tsqn202103110);山东省青创人才引育计划(10073004);山东省重点研发计划项目(2021CXGC010511)
UHPLC-HRMS Identification and Analysis of the Metabolites in Vivo of Isoimperatorin in Rats
WANG Hong1,2, CUI Yifang2, XU Jing2, LI Yanan2, LIN Yongqiang3, LI Qiyan3, ZHANG Jiayu1
1.College of Pharmacy, Binzhou Medical University, Binzhou 264003, China;2.School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250300, China;3.Shandong Institute for Food and Drug Control, Jinan 250101, China
Abstract:
OBJECTIVE To analyze and identify the metabolites of isoimperatorin in normal rats in vivo. METHODS After the rats were intragastrically administered, the plasma, urine and feces samples of rats in normal and dosed groups were collected, and the samples were processed by solid phase extraction. Then, UHPLC-HRMS(Q-Exactive Orbitrap MS) high- resolution mass spectrometry was used to analyze biological samples, and the metabolites were screened and identified. RESULTS In both positive and negative ion modes, a total of 32 metabolites were accurately analyzed and identified based on the precise molecular masses obtained, chromatographic retention behavior, control mass spectral cleavage patterns, characteristic fragment ions, and relevant literature reports. The main metabolic pathways were furan ring opening, lactone hydrolysis, oxidation, methylation, glucuronidation, sulfation and their complex reactions. Among them, the glucuronidation product was discovered for the first time. CONCLUSION This study comprehensively clarifies the transformation pathways of isoimperatorin in rats, which can provide a basis for its pharmacodynamic study and metabolism study analysis of the other furocoumarins.
Key words:  isoimperatorin  metabolism in vivo  UHPLC-HRMS(Q-Exactive Orbitrap MS)  metabolites
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