目的 基于超高效液相色谱-四极杆-飞行时间串联质谱（UPLC-Q-TOF-MS/MS）技术分析虎杖二金汤化 学成分及其在胆汁淤积小鼠体内的入血成分和代谢原型成分。方法 采用灌胃 α-萘异硫氰酸酯（ANIT）大豆油 溶液构建胆汁淤积小鼠模型。将 36 只 C57BL/6 雄性小鼠随机分为正常组、模型组、空白给药组、模型给药 组，每组 9 只。空白给药组和模型给药组灌胃虎杖二金汤提取物（7.2 g·kg -1 ），模型组、正常组灌胃等量纯水， 每天 1 次，连续给药 7 d。采用试剂盒法检测小鼠血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶 （AST）、总胆汁酸（TBA）、总胆红素（TBIL）水平，并结合肝脏 HE 染色病理切片观察虎杖二金汤干预胆汁淤积 的效果。采用 UPLC-Q-TOF-MS/MS 技术，以乙腈-甲酸水溶液为流动相进行梯度洗脱，在正、负离子模式下 扫描获得一、二级质谱信息，参照相关文献信息，鉴定虎杖二金汤的化学成分，并进一步分析虎杖二金汤在正常 和胆汁淤积小鼠体内的入血原型成分和代谢产物。结果 药效学结果显示，虎杖二金汤降低了胆汁淤积小鼠血清 ALT、AST、TBA、TBIL 水平（P＜0.05，P＜0.01），改善了其肝脏的病理结构损伤，对小鼠胆汁淤积具有显著 的缓解作用。在虎杖二金汤中鉴别出 70 个化学成分，主要包括蒽醌类、二苯乙烯类、倍半萜类成分等。在正 常（空白给药组）和胆汁淤积（模型给药组）小鼠血清中共鉴定出虎杖二金汤中 13 个原型成分和 51 种代谢产物， 原型成分主要发生Ⅰ相代谢反应，主要涉及氧化、水解、脱氧等反应；部分Ⅱ相代谢产物主要涉及甲基化、葡 萄糖醛酸化等反应。正常和胆汁淤积小鼠血清中均可检测到白藜芦醇及其代谢产物，且胆汁淤积小鼠血清中白 藜芦醇及其代谢产物含量较正常小鼠有增加趋势，但差异无统计学意义（P＞0.05）。胆汁淤积小鼠血清中大黄 素和大黄素甲醚的含量均较正常小鼠明显增加（P＜0.01），且胆汁淤积小鼠血清中大黄素甲基化和葡萄糖醛酸 化的代谢产物含量也均较正常小鼠增加（P＜0.01）。结论 UPLC-Q-TOF-MS/MS 技术能实现虎杖二金汤的化学 成分及其入血原型成分和代谢产物的快速分析。白藜芦醇、大黄素、大黄素甲醚和大黄素-8-O-β-D-葡萄糖 苷可能是虎杖二金汤潜在的关键药效成分，可为虎杖二金汤的药效物质基础和质量标志物研究提供实验依据。

Objective To analyze the chemical constituents of Huzhang Erjin Decoction （HZEJD） and identify its prototype components and metabolites in the serum of cholestatic mice using ultra performance liquid chromatography-quadrupole time of light tandem mass spectromety （UPLC-Q-TOF-MS/MS） technology. Methods A cholestatic mouse model was established by intragastric administration of α-naphthylisothiocyanate （ANIT） soybean oil solution. Thirty- six C57BL/6 male mice were randomly divided into normal group，model group，blank administration group，and model administration group， with nine mice per group. The blank administration and model administration groups received HZEJD extract （7.2 g·kg -1 ） via gavage，while the model and normal groups received an equal volume of pure water once daily for seven consecutive days. Serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST），total bile acid （TBA），and total bilirubin （TBIL） were measured using assay kits，and liver histopathological changes were observed via HE staining to evaluate the interventive effects of HZEJD on cholestasis. UPLC-Q-TOF-MS/MS analysis was performed using acetonitrile-formic acid aqueous solution as the mobile phase for gradient elution. Primary and secondary mass spectrometry data were acquired in positive and negative ion modes. Chemical constituents of HZEJD were identified by referencing relevant literature， and prototype components and metabolites of HZEJD in the serum of normal and cholestatic mice were further analyzed. Results Pharmacodynamic results showed that HZEJD reduced serum levels of ALT，AST，TBA，and TBIL in cholestatic mice，ameliorated liver histopathological damage， and significantly alleviated cholestasis. Seventy chemical constituents were identified in HZEJD， primarily including anthraquinones， stilbenes， and sesquiterpenes. Thirteen prototype components and 51 metabolites of HZEJD were identified in the serum of both normal （blank administration group） and cholestatic （model administration group） mice. Prototype components mainly underwent Phase Ⅰ metabolic reactions，including oxidation，hydrolysis，and deoxygenation. Some Phase Ⅱ metabolites primarily involved methylation and glucuronidation. Resveratrol and its metabolites were detected in the serum of both normal and cholestatic mice，with a trend toward increased levels in cholestatic mice，though the difference was not statistically significant （P＞0.05）. The serum levels of emodin and physcion were significantly increased in cholestatic mice compared to normal mice （P＜0.01）. Metabolites of emodin methylation and glucuronidation were also significantly elevated in cholestatic mice （P＜0.01）. Conclusion UPLC-Q-TOF-MS/MS technology enables rapid analysis of the chemical constituents of HZEJD and its prototype components and metabolites in serum. Resveratrol，emodin，physcion，and emodin-8-O-β-D-glucoside may be potential key pharmacodynamic components of HZEJD， providing an experimental basis for elucidating its material foundation and discovering quality markers.

R284.1，R285.5

国家自然科学基金项目（82204967）；广东省基础与应用基础研究基金项目（2025A1515012896）；广州市科技计划项目（2025A04J3936）； 广州中医药大学校院联合科技创新基金项目（GZYZS2024G03）。