目的 运用UHPLC-Q-Exactive Orbitrap HRMS技术实现高效、快速、精准分析鉴定黄连解毒汤的化学成分及大鼠ig后其主要成分在不同组织中的分布。方法 色谱分离采用Acquity UPLC BEH C₁₈色谱柱(100mm×2.1mm,1.7μm),以0.1%甲酸水溶液-甲醇为流动相梯度洗脱,通过HRMS的正、负离子监测模式,全扫描及自动触发二级质谱扫描功能(Full MS/dd-MS²),对黄连解毒汤中的化学成分进行快速分析及鉴定。在此基础上,对大鼠口服黄连解毒汤后血及组织中的移行成分进行鉴定。结果 通过化合物的一级、二级质谱信息,结合对照品比对确认与相关文献报道分析,从黄连解毒汤中共鉴定出110种化学成分,包括36种黄酮类、28种环烯醚萜、15种生物碱、15种有机酸、5种木脂素以及11种其他类化合物。大鼠ig黄连解毒汤后,分别从血清、心、肝、脾、肺、肾、脑、睾丸中检测到40、50、55、65、61、62、32、46种原型成分。根据各原型成分在原方、血清及各组织中的均一化峰面积,可知栀子新苷、黄连碱、小檗碱、巴马汀、药根碱、黄柏碱等成分在肝、肾等组织中有较大的暴露量。结论 借助UHPLC-Q-Exactive Orbitrap HRMS技术系统、准确、快速地实现了黄连解毒汤化学成分鉴定,并揭示了黄连解毒汤大鼠ig给药后主要成分的组织分布特征,为后续黄连解毒汤潜在药效物质基础研究及临床应用提供参考。

Objective The UHPLC-Q-Exactive Orbitrap HRMS technology was used to efficiently, quickly and accurately analyze and identify the chemical components of Huanglian Jiedu Decoction (HJD, 黄连解毒汤) and the distribution of its main components in different tissues after oral administration in rats. Method An Acquity UPLC BEH C₁₈ column (100 mm×2.1 mm, 1.7 μm) was used for chromatographic separation, with 0.1% formic acid aqueous solution-methanol as mobile phase gradient elution. Chemical constituents in HJD were rapidly isolated and identified by HRMS in the positive and negative ion mode with both full scan and two stage threshold-triggered mass modes (Full MS/dd-MS²). On this basis, the transitional components in the blood and tissues of rats after oral administration of HJD were identified. Results A total of 110 chemical constituents were identified from Huanglian Decoction Soup, including 36 kinds of flavonoids, 28 kinds of iridoids, 15 kinds of alkaloids, 15 kinds of organic acids, 5 kinds of lignans, and 11 kinds of other compounds, by the primary and secondary mass spectrometry information of the compounds, combined with the confirmation of the retention times and MS/MS spectra of the standards by comparison and analysis of related literature. After oral administered HJD to rats, 40, 50, 55, 65, 61, 62, 32, 46 prototype compounds were detected in serum, heart, liver, spleen, lung, kidney, brain, and testicles, respectively. According to the homogenization peak area of each prototype component in the extract, serum and tissues, it can be known that gardoside, coptisine, berberine, palmatine, jatrorrhizine, phellodendrine have large exposure in liver, kidney, and other tissues. Conclusion With the help of,UHPLC-Q-Exactive Orbitrap HRMS method, the identification of the constituents in HJD was systematically, accurately and rapidly achieved, and the tissue distribution of main components were investigated in rats following oral administration of HJD. These findings provided key information and guidance for further studies on pharmacodynamic substances and clinical applications of HJD.

R284.1

国家自然科学基金项目（81703681）；中国科协青年托举工程项目（2020QNRC001）；上海市教育委员会和上海市教育发展基金会“晨光计划”项目（20CG50）；上海市科技创新行动计划项目（20S21902600）；上海市科技创新行动计划项目（19401972700）