Zheng Ting, Zhao Yue, Li Ruijuan, Huang Mengwen, Zhou An, Li Zegeng, Wu Huan
Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, China.
J Pharm Anal. 2022 Oct;12(5):755-765. doi: 10.1016/j.jpha.2022.05.005. Epub 2022 May 21.
Qi-Yu-San-Long decoction (QYSLD) is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer (NSCLC) for more than 20 years. However, to date, metabolic-related studies on QYSLD have not been performed. In this study, a post-targeted screening strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight full information tandem mass spectrometry (UPLC-QTOF-MS) was developed to identify QYSLD-related xenobiotics in rat urine. The chemical compound database of QYSLD constituents was established from previous research, and metabolites related to these compounds were predicted in combination with their possible metabolic pathways. The metabolites were identified by extracted ion chromatograms using predicted / values as well as retention time, excimer ions, and fragmentation behavior. Overall, 85 QYSLD-related xenobiotics (20 prototype compounds and 65 metabolites) were characterized from rat urine. The main metabolic reactions and elimination features of QYSLD included oxidation, reduction, decarboxylation, hydrolysis, demethylation, glucuronidation, sulfation, methylation, deglycosylation, acetylation, and associated combination reactions. Of the identified molecules, 14 prototype compounds and 58 metabolites were slowly eliminated, thus accumulating in vivo over an extended period, while five prototypes and two metabolites were present in vivo for a short duration. Furthermore, one prototype and five metabolites underwent the process of "appearing-disappearing-reappearing" in vivo. Overall, the metabolic profile and characteristics of QYSLD in rat urine were determined, which is useful in elucidating the active components of the decoction in vivo, thus providing the basis for studying its mechanism of action.
芪榆三龙汤（QYSLD）是一种已临床应用20多年来治疗非小细胞肺癌（NSCLC）的中药。然而，迄今为止，尚未对QYSLD进行代谢相关研究。在本研究中，开发了一种基于超高效液相色谱-四极杆飞行时间全信息串联质谱（UPLC-QTOF-MS）的靶向筛选策略，以鉴定大鼠尿液中与QYSLD相关的外源性物质。根据先前的研究建立了QYSLD成分的化合物数据库，并结合其可能的代谢途径预测了与这些化合物相关的代谢产物。通过使用预测的/值以及保留时间、准分子离子和碎片行为的提取离子色谱图来鉴定代谢产物。总体而言，从大鼠尿液中鉴定出85种与QYSLD相关的外源性物质（20种原型化合物和65种代谢产物）。QYSLD的主要代谢反应和消除特征包括氧化、还原、脱羧、水解、去甲基化、葡萄糖醛酸化、硫酸化、甲基化、去糖基化、乙酰化以及相关的结合反应。在鉴定出的分子中，14种原型化合物和58种代谢产物消除缓慢，因此在体内长时间积累，而5种原型化合物和2种代谢产物在体内存在时间较短。此外，一种原型化合物和5种代谢产物在体内经历了“出现-消失-再出现”的过程。总体而言，确定了QYSLD在大鼠尿液中的代谢谱和特征，这有助于阐明该汤剂在体内的活性成分，从而为研究其作用机制提供依据。
