New analytical method for determination of epimer metabolites in rat plasma after oral administration of Paeoniflorin by UPLC-TOF-MS following picolinoyl derivatization

Abstract A highly sensitive analytical method was developed to study the in vivo metabolism of paeoniflorin, one of the most principal components in traditional Chinese medicine. After hydrolyzation with sulfatase, the epimer metabolites 7S-paeonimetabolin I and 7R-paeonimetabolin I of paeoniflorin in rat plasma were successfully detected and well separated by LC–MS following picolinoyl derivatization for the first time. Borneol was used as the internal standard to quantify 7S-paeonimetabolin I and 7R-paeonimetabolin I in rat plasma. 7S-paeonimetabolin I and 7R-paeonimetabolin I show similar but different pharmacokinetic behavior. 7S-paeonimetabolin I reached the maximum mean plasma concentration of 45.7 ± 4.6 ng/mL at about 1.5 h after oral administration of paeoniflorin at a dose of 5 mg/kg, while 7R-paeonimetabolin I reached the maximum mean plasma concentration of 39.2 ± 3.5 ng/mL at about 1.5 h. The full metabolic pathway of paeoniflorin in rats was proposed. The monoterpene compound paeoniflorin was found to be metabolized to the sulfate of 7S-paeonimetabolin I and 7R-paeonimetabolin I in vivo which maybe responsible for the pharmacological effect of paeoniflorin.