目的 采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱技术（UHPLC-Q-Exactive MS）分析、筛选、鉴定桔红素在大鼠体内的代谢产物。方法 大鼠ig给予桔红素溶液后，收集不同时间点的血浆及24 h内的尿液与粪便，经固相萃取法处理后，使用Acquity UPLC BEH C₁₈色谱柱（100 mm×2.1 mm，1.7 μm）和0.1%甲酸水溶液（A）-乙腈（B）流动相系统进行梯度洗脱，在正离子扫描模式下分析给药组大鼠的生物样品。结果 通过检索化合物的多级质谱信息，由精确相对分子质量推测分子式，结合对照品的特征性裂解规律，共鉴定出包括桔红素在内的28个代谢产物。结论 桔红素在大鼠体内主要发生去甲基化、羟基化、硫酸酯化、葡萄糖醛酸化、去甲氧基化、甲氧基化、脱一氧化碳以及它们的复合反应等。较为详细地阐明了桔红素在大鼠体内的代谢情况，剖析了其代谢过程，可为其进一步的药效学、药动学及毒理学研究提供参考。

Objective Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive MS) was used to analyze, screen and identify the metabolites of tangeretin in rats. Methods The plasma at different time points and urine and feces within 24 h were collected after the rats were given tangeretin solution by gavage. After solid phase extraction (SPE) treatment, the gradient elution was carried out on the Acquity UPLC BEH C₁₈column (100 mm×2.1 mm, 1.7 μm) with 0.1% formic acid solution (A)-acetonitrile (B) mobile phase system. The biological samples of the rats in the drug group were analyzed in the positive ion scanning mode. Results By retrieving the multi-level mass spectrometry information of the compound, inferring the molecular formula from the accurate relative molecular mass, and combining with the characteristic cleavage law of the reference standard, a total of 28 metabolites including tangeretin were identified. Conclusion The results showed that tangeretin mainly underwent demethylation, hydroxylation, sulfonation, glucuronidation, demethoxylation, methoxylation, carbon monoxide removal, and their composite reactions in rats. Therefore, this study had elucidated the metabolism of tangeretin in rats in detail and analyzed its metabolic process, which could provide reference for further pharmacodynamics,pharmacokinetics and toxicology research.

R284.1

江苏省中药药效与安全性评价重点实验室项目（JKLPSE201816）；中医脑病学山西省重点实验室（山西中医药大学）项目（CME-OP-2017002）；国家药典委员会项目（2018Y007）