Kinetic features of Gualou-Xiebai-Banxia decoction, a classical traditional Chinese medicine formula, in rat plasma and intestine content based on its metabolic profile

Gualou-Xiebai-Banxia decoction (GXB) is a famous classical traditional Chinese medicine (TCM) formula for the treatment of coronary heart disease (CHD, namely chest stuffiness and pain syndrome in Chinese medicine). Compared with Gualou-Xiebai-Baijiu decoction, which only consists of Trichosanthis Pericarpium (TP), Allii Macrostemonis Bulbus (AMB) and wine, GXB comprises one additional herbal medicine, Pinellinae Rhizoma Praeparatum (PRP). However, due to a lack of kinetic profile studies on GXB, its in vivo components with high exposure remain unknown, making it difficult to interpret bioactive components likely linked to its efficacy, but also fails to provide substance-related evidence for reflecting the compatibility in GXB. The goal of this study was to systematically characterize the kinetic features of GXB in rat plasma and intestine content for revealing its in vivo high-exposure components on the basis of their metabolic fates, and to compare the kinetic differences between GXB and GXB-dePRP (GXB deducted PRP) for describing the chemical contribution of PRP to the compatibility in GXB. Firstly, the metabolic profile of GXB was systematically investigated by UPLC-Q/TOF-MS. Subsequently, quantitative methods for representative xenobiotics in rat plasma and intestine content were respectively validated and developed by UPLC-TQ-MS. Then, the established approaches were successfully applied to characterize the kinetic features of GXB through estimating pharmacokinetic parameters. These results showed that only a few kinds of xenobiotics at low exposure levels were observed in plasma, while various xenobiotics possessed high exposure in intestine content. Among them, steroidal saponins and triterpenoid saponins displayed relatively high exposure in plasma and intestine content, which are likely associated with the therapeutic effects of GXB. Moreover, there were no significant differences between metabolic profiles of GXB and GXB-dePRP, whereas the pharmacokinetic parameters, including area under the concentration–time curve (AUC) and C max ( p  < 0.05) for most xenobiotics in GXB were significantly larger than those in GXB-dePRP, implying that the introduction of PRP improved the bioavailability of constituents from TP and AMB. Altogether, this study laid a solid foundation and provided theoretical guidance for further clarification of bioactive components of GXB, as well as the synergistic effect of PRP to the compatibility in GXB.