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芦丁在大鼠体内的代谢产物鉴定与代谢途径分析 被引量:1

Identification of rutin metabolites and analysis of rutin metabolic pathway in rats
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摘要 分析大鼠口服芦丁后血浆、尿液和粪便中的代谢产物并评价芦丁在大鼠体内的代谢途径。大鼠灌胃给予250 mg/kg芦丁后,采集血浆、尿液和粪便,以固相萃取法处理生物样品,利用超高效液相色谱-四级杆-静电场轨道阱质谱,以0.05%甲酸水(A)-0.05%甲酸乙腈(B)为流动相梯度洗脱,分别在正、负离子模式下采集各样品数据,通过高分辨提取离子流图和平行反应监测模式,结合色谱保留时间、质量测量、诊断离子等确定芦丁的代谢物并探究芦丁在大鼠体内的代谢途径。在正、负离子模式下共检测和鉴定了29种芦丁代谢产物,其主要代谢途径为甲基化、葡萄糖醛酸化、硫酸酯化及其复合反应等。建立了芦丁的整体代谢图谱,为其进一步的药效学评价及开发利用提供了参考依据,同时也为药物代谢鉴定研究提供了一种综合研究方法。 Herein,metabolites in plasma,urine and feces of rats were analyzed after oral administration of rutin and the metabolic pathway of rutin was evaluated.After intragastric administration of 250 mg/kg rutin,plasma,urine,and feces were collected and treated via solid phase extraction.Ultra-high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrapmass spectrometry(UPLC-Q-Orbitrap MS)was used with 0.05%formic acid water(A)-0.05%formic acid acetonitrile(B)as mobile phase gradient elution.The sample data were collected in positive-and negative-ion modes.The metabolites and metabolic pathway of rutin in rats were determined via high resolution extraction ion chromatography in the parallel reaction monitoring mode,combined with chromatographic retention time,accurate mass measurement and diagnostic ions.Twenty-nine rutin metabolites were detected and identified in positive and negative ion modes,and their main metabolic pathways were methylation,glucuronidation,sulfation and their compound reaction.The study provided the overall metabolic profile of rutin,which will provide a reference for further pharmacodynamic evaluation,development,and utilization in the future and offer a comprehensive research method for drug metabolism identification.
作者 王常瞵 高明周 郭英慧 孙亚 于小钧 闫志 王杰琼 乔明琦 WANG Changlin;GAO Mingzhou;GUO Yinghui;SUN Ya;YU Xiaojun;YAN Zhi;WANG Jieqiong;QIAO Mingqi(School of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Institute of Traditional Chinese Medicine Innovation,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)
出处 《山东科学》 CAS 2023年第5期9-18,共10页 Shandong Science
基金 国家自然科学基金面上项目(81473558) 山东省自然科学基金(ZR202102270167) 山东省自然科学基金重点项目(ZR2020ZD17) 国家科技重大专项(重大新药创制)(SQ2017ZX091064) 山东省医药卫生科技发展计划(202105010467)。
关键词 芦丁 超高效液相色谱-四级杆-静电场轨道阱质谱 代谢产物 代谢途径 rutin UPLC-Q-Orbitrap MS metabolites metabolic pathways
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