Simultaneous Determination of Four Bioactive Flavonoids in Rat Plasma by UPLC-MS/MS and Comparative Pharmacokinetic Study after Oral Administration of Danyikangtai Powder and Three Compatibilities

Background: Danyikangtai powder, a Traditional Chinese Medicine (TCM) formula, shows promise to become a novel drug candidate for the simultaneous treatment of chronic cholecystitis and chronic pancreatitis. However, the pharmacokinetic behavior of Danyikangtai powder remains unclear. Objective: We investigated the comparative pharmacokinetics of four flavonoids in rats after oral administration of Danyikangtai powder and three compatibilities. Materials and Methods: The comparative pharmacokinetics was studied by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS). Chromatographic separation was performed on a Universil XB-C18 column with a gradient mobile phase containing 0.1% (v/v) aqueous formic acid and acetonitrile. All analytes and internal standard were quantitated in the multiple reaction monitoring modes with a positive electrospray ionization interface. Results and Discussion: Danyikangtai powder and Scutellariae radix have similar pharmacokinetic behaviors in rats after oral administration. However, the elimination of four flavonoids in rats after oral administration of Danyikangtai powder was accelerated, which was possibly related to the reduction of the potential hepatotoxicity of Scutellariae radix. The varying degrees of change in pharmacokinetic parameters after oral administration of different herb combinations suggested that herb–herb interactions occurred in vivo. Conclusions: This study will be helpful to reveal the safety, rational and mechanism of Danyikangtai powder formula compatibility, thereby providing pre-clinical research data for its new drug development and guidance for its rational clinical application.