中草藥 2023年9月 第54卷 第17期
Abstract: Objective To identify the metabolites of 5,7-dimethoxycoumarin and 6,7-dimethoxycoumarin in plasma, tissues (heart, liver, spleen, lung, kidney, stomach and small intestine), urine and feces in rats by using hybrid quadrupole-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Methods SD male rats were ig 5,7-dimethoxycoumarin and 6,7 dimethoxycoumarin (100 mg/kg), the plasma, tissue, urine, and fecal samples were collected. After sample pretreatment, a Thermo Scientific AccucoreT M C18 column (100 mm × 3 mm, 2.6 μm) was used, the gradient elution was performed with 0.1% formic acid- 0.1% formic acid acetonitrileas the mobile phase. The mass spectrometry data of biological samples were acquired in positive ion mode with an electrospray ionization source (ESI source). Xcalibur was used to collect data, and the compound metabolite prediction template of Compound Discoverer 3.1 software was used for analysis, and the metabolites were identified in combination with relevant literature and Mass Frontier 7.0 software. Results A total of 33 5,7-dimethoxycoumarin metabolites and 21 6,7-dimethoxycoumarin metabolites were detected in biological samples from rats. A total of 8, 28, 23, 2, 10, 3, 10, 13, 7, 7 metabolites of 5,7 dimethoxycoumarin and 7, 19, 14, 7, 7, 4, 7, 13, 3, 8 metabolites of 6,7-dimethoxycoumarin were identified in plasma, urine, feces, heart, liver, spleen, lung, kidney, stomach and small intestine, respectively. Conclusion A total of 33 metabolites of 5,7 dimethoxycoumarin and 21 metabolites of 6,7-dimethoxycoumarin were identified by liquid chromatography-mass spectrometry. The metabolism of the two coumarins in rats was elucidated through demethylation, hydroxylation, hydrolysis, reduction, methylation, sulfation and glucuronidation. The metabolic characteristics of the two coumarins were compared and analyzed. This study laid a foundation for further study on the mechanism and pathway of action of the two coumarin in traditional Chinese medicine, and also provided a comprehensive research method for drug metabolism identification.
Key words: UHPLC-Q-Orbitrap HRMS; 5,7-dimethoxycoumarin; 6,7-dimethoxycoumarin; metabolites; metabolic pathway
本研究中對照品：5,7-二甲氧基香豆素（批號 1211325801）、6,7-二甲氧基香豆素（批號 1211201901）均購自于四川恒誠致遠生物科技有限公司（Naturewill biotechnology Co., Ltd.）
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