目的 基于序贯代谢方法结合超高效液相色谱-四极杆-轨道阱-线性离子阱质谱(UPLC-Q-OT-qIT MS)联用技术,系统分析一枝蒿提取物及其肠代谢、肝代谢和综合代谢产物,全面表征其入血原型成分及体内代谢转化规律。方法 制备一枝蒿提取物,通过肠灌流收集肠壁代谢、肠道菌群代谢、肝代谢的血浆样本,ig给药收集综合代谢血浆样本,结合UPLC-Q-OT-qIT MS对各个样本所含成分进行分析与鉴定。结果 从一枝蒿提取物中共发现黄酮类、倍半萜类、有机酸类等53个化学成分。在肠代谢样品中发现43个原型入血成分和20个代谢产物,肝代谢样品中发现28个原型入血成分和20个代谢产物,综合代谢组样品中发现18个原型入血成分和17个代谢产物。结论 基于序贯代谢研究,系统探究一枝蒿于大鼠体内的代谢规律,鉴定其原型入血成分及代谢产物,揭示不同代谢部位的成分差异及生物转化过程,为明确一枝蒿药效物质基础及其质量标准提升提供科学依据与数据支持。

Objective To systematically analyze the extract of Artemisia rupestris and its intestinal metabolism, liver metabolism and comprehensive metabolic products based on sequential metabolic method combined with ultra-high performance liquid chromatography-quadrupole-Orbitrap-linear ion trap mass spectrometry (UPLC-Q-OT-qIT MS) joint technology, and fully characterize its blood-entering prototype components and the regularity of in vivo metabolic transformation. Methods The extract of A. rupestris was prepared, and after in vitro intestinal perfusion, plasma samples of intestinal wall metabolism, intestinal flora metabolism and liver metabolism were separately collected. After intragastric administration, comprehensive metabolic plasma samples were collected. The components contained in each sample were analyzed and identified by UPLC-Q-OT-qIT MS. Results A total of 53 chemical components including flavonoids, sesquiterpenes and organic acids, were detected in the extract of A. rupestris. A total of 43 prototype blood-entering components and 20 metabolites were detected in the intestinal metabolism samples, 28 prototype blood-entering components and 20 metabolites were detected in the liver metabolism samples, and 18 prototype blood-entering components and 17 metabolites were detected in the comprehensive metabolic group samples. Conclusion Based on the sequential metabolic method, the metabolic patterns of A. rupestris in rats were systematically analyzed, its prototype blood-entering components and metabolites were identified, and the differences in components among different metabolic sites and the biological transformation process were revealed, providing a scientific basis and data support for clarifying the pharmacodynamic material basis of A. rupestris and improving its quality standards.

R285.61

新疆维吾尔自治区重点研发计划项目（2023B03012-2）；新疆维吾尔自治区公益性科研院所基本科研业务经费资助项目（KY2025088）；新疆维吾尔自治区自然科学基金-杰出青年项目（2021D01E25）