Dingkun Dan (DKD), a reputable traditional Chinese medicine formula, has been used to treat gynecological disease and showed significant clinical effect since ancient times. However, the application and development of DKD is seriously hampered by the unclear active substances. Structural characterization of compounds absorbed in vivo and their corresponding metabolites is significant for clarifying the pharmacodynamic material basis. In this study, an integrated strategy by using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and UNIFI™ software was used to identify prototypes and metabolites after oral administration of DKD in rats. As a result, a total of 261 compounds, including 140 prototypes and 121 metabolites, were tentatively characterized in rat plasma, urine and feces. The metabolic pathways of prototypes have been studied to clarify their possible transformation process in vivo. Moreover, an in vitro metabolism study was applied for verifying the metabolites under simulating the metabolic environment in vivo. This first systematic metabolic study of DKD is important for elucidating the metabolites and metabolic pathways, and could provide a scientific basis for explaining integrative mechanism in the further pharmacology study.
crocin I, crocin II, tetrahydropalmatine, saikosaponin A, saikosaponin b2, genkwanin, akebia saponin D were purchased from Chengdu Biopurify Phytochemicals
Ltd (Sichuan, China).
