Metabolic profile of Yi-Xin-Shu capsule in rat by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry analysis

Yi-Xin-Shu capsule (YXS), a Chinese patented medicine, is widely used for treating coronary heart disease. However, due to the lack of studies on chemical and systematic metabolic profiling, the active substances and metabolic fate of YXS were still unknown, which became a huge obstacle for the clinical-safe medication administration and the quality control of YXS. To solve this problem, the investigation of the metabolic profiles of YXS in rat plasma, urine and feces was conducted. To completely identify the predictable and unpredictable metabolites, a combined data mining strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF MS) was employed. As a result, a total of 184 compounds were tentatively identified in rat biological fluids after oral administration of YXS, including 143 compounds in plasma, 82 compounds in urine and 116 compounds in feces. Among them, 11 lignan-related metabolites were identified for the first time, and the metabolite pathways were tentatively proposed in this study. In addition, based on the identified tanshinone-related metabolites, the metabolite pathways of tanshinones were tentatively proposed for the first time. Furthermore, the results indicated that ginsenosides, lignans and tanshinones were the major absorbed chemical components of YXS. From the total numbers of compounds detected in urine and feces, we considered that many more compounds were cleared through feces. Oxidation reactions as well as hydrolysis reactions were the major metabolic reactions in vivo. This study is the first to report the description of YXS metabolism in vivo. The metabolite profile analysis of YXS in different biological fluids provided a comprehensive understanding of the in vivo metabolic fates of constituents in YXS.