State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Sep 1;1125:121721. doi: 10.1016/j.jchromb.2019.121721. Epub 2019 Jul 17.
Tripterygium glycosides tablets (TGT) contain the main extract of tripterygium and are widely used clinically to treat autoimmune diseases such as rheumatoid arthritis and nephrotic syndrome. However, TGT can lead to liver and renal failure in clinic. The exposed components and their metabolites of TGT in vivo were rarely researched. In this study, the components and metabolites of TGT in mice liver, kidney and plasma were profiled by high performance liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry (HPLC-Q/TOFMS) after TGT was orally administered to mice. The components and metabolites were detected and identified based on their retention time, accurate mass data of quasi-molecular ion, characteristic fragment ions, and the fragmentation rules. Finally, 48 prototype components, including 25 diterpenoids, 11 triterpenoids and 12 alkaloids, were detected in mice, as well as 99 metabolites, undergoing hydroxylation, dehydrogenation, ester bond hydrolysis of Phase I metabolism, and glutathione, glucuronic acid binding of Phase II metabolism. The components and metabolites in mice were compared between single- and multiple- low dose groups and between high and low dose groups. Furthermore, a total of 21 components and 35 metabolites were predicted to have potential toxic risk by software. The results would provide material basis to clarify the clinical efficacy and toxicity of TGT.
雷公藤多苷片(TGT)含有雷公藤的主要提取物,临床上广泛用于治疗类风湿关节炎和肾病综合征等自身免疫性疾病。然而,TGT 会导致临床肝肾功能衰竭。TGT 在体内的暴露成分及其代谢物很少被研究。本研究采用高效液相色谱-串联四极杆飞行时间质谱(HPLC-Q/TOFMS)法分析了 TGT 灌胃给药后小鼠肝、肾和血浆中的成分和代谢物。基于保留时间、准分子离子的精确质量数据、特征碎片离子和裂解规律,对成分和代谢物进行了检测和鉴定。最终,在小鼠体内检测到 48 个原型成分,包括 25 个二萜、11 个三萜和 12 个生物碱,以及 99 个代谢物,经历了 I 相代谢的羟化、脱氢、酯键水解,以及 II 相代谢的谷胱甘肽、葡萄糖醛酸结合。比较了单低、多低剂量组以及高低剂量组之间的小鼠成分和代谢物。此外,有 21 个成分和 35 个代谢物被软件预测具有潜在毒性风险。该研究结果将为阐明 TGT 的临床疗效和毒性提供物质基础。