LAUSR

HighlightsIt's the first time that the in vivo multiple absorbed and metabolic components of Caulopphyllum Robustum after oral administration have been comprehensively revealed.The cracking model of biological samples in the effective part of Caulopphyllum Robustum was built in the negative ion mode.The metabolic pathways of Cauloside C, Cauloside D, Leonyicin D and Cauloside H in rats were proposed, and they were identified as a phenomenon of mutual transformation in vivo exsited.The identification of metabolites was achieved using UPLC‐LTQ Qrbitrap MS and took powerful supplement information to the subsequent study. ABSTRACT Triterpenoid saponins are the main bioactive components in Caulopphyllum Robustum Maxim (CRM), and they have been reported to have extensive pharmacological properties, such as anti‐inflammatory, immunomodulatory, and anti‐tumor effects. Cauloside C, Cauloside D, Leonticin D and Cauloside H are the main active chemical constituents of CRM in the treatment of rheumatoid arthritis (RA). However, their metabolic processes and products remain unclear. Therefore, the purpose of this study was to analyze the metabolic components and metabolic pathways of total saponins after oral administration of CRM effective part (CRME) in rats. In this work, we collected plasma, bile, urine and feces of rats at different sampling time points after intragastric administration. The saponins and reference substances were separated from CRME and analyzed via Thermo Scientific™ Ultra Performance Liquid Chromatography‐Orbitrap Elite Combined High resolution Mass Spectrometry. According to the structural characteristics of the compounds in CRM, the pyrolysis behavior of various components was inferred in the negative ion mode. Twenty‐two components were found in rat plasma, bile, urine and stool; among these components, there were 8 prototypes and 14 metabolites. Seven prototypes and 8 metabolites were found in rat plasma; no prototype and 6 metabolites were found in bile; 5 prototypes and 8 metabolites were found in urine; and 4 prototypes and 9 metabolites were found in stool. The metabolites include deglycosylation products, sapogenin products, sulfides, and glucuronide conjugates. The same metabolites were also found in biological samples, and these products may be important metabolic pathways of triterpene saponins in rats. The current findings clarified the metabolic pathways of the main active ingredients in CRME and further elucidated the anti‐RA drug‐responsive substance basis of CRM.