A combination of representative compounds, metabolism platform and diagnostic extraction strategy for characterization of metabolites of Shuang-Huang-Lian oral liquid in vivo by ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry.

Traditional Chinese medicines (TCMs) usually contained a large number of chemical components, which could be transformed into more complex metabolites in vivo. In this work, a "Representative compounds-Metabolism platform-Diagnostic extraction" strategy (RMD strategy) was proposed for comprehensively identification or characterization of xenobiotics in rat after oral administration of TCMs. Shuang-Huang-Lian oral liquid (SHL), a well-known traditional Chinese medicine preparation, was used as an example. The metabolic pathways of six representative compounds, bearing five different core structures in SHL, were elucidated and their metabolic reactions were employed for exploring metabolites of homologous components in metabolism platform. Meanwhile, diagnostic ions extraction were also used for screening more structural analogues in biofluids. All this work was completed by ultra-performance liquid chromatography coupled electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/Qtof MS) and UNIFI metabolism platform. As a result, a total of 254 xenobiotics were identified or tentatively characterized in rat plasma and urine after oral administration of SHL and six representative compounds. The metabolism reaction included phase I reaction (hydroxylation, hydrolysis reaction, deglycosylation, hydrogenation, demethylation, dehydroxylation and ring opening reaction) and phase II reaction (glucuronidation, sulfation and methylation). This research provided useful information for further study of the pharmacology and mechanism of SHL in vivo. It also demonstrated that RMD strategy was an efficient approach for facilitate screening-out and rapid identification of xenobiotics in biological samples after oral administration of TCMs.