Comparative Pharmacokinetic Studies of Paeoniflorin, Albiflorin and Oxypaeoniflorin Between Normal and Cerebral Ischemia–Reperfusion Rats Based on the Simultaneous Determinations Using an UPLC-MS–MS Method

Abstract

To explore the pharmacokinetic characteristics of the three monoterpene glycosides (paeoniflorin, albiflorin and oxypaeoniflorin) extracted from the Radix Paeoniae Rubra (RPR), we determined the plasma concentrations of these components in the cerebral ischemia–reperfusion (CIR) rats and the normal rats by a self-developed and validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS–MS) method. In this study, the CIR rats and the normal rats both underwent an intravenous administration of total paeony glucosides (TPG). The blood samples were collected from rats by eye puncture at a series of time points. Then, the pharmacokinetic parameters of the three components were calculated, including the half-life (t1/2), the area under curve of the concentration–time (AUC), the mean residence time (MRT), apparent volume of distribution (Vz) and the clearance (CL). Studies demonstrated that the Vz of albiflorin, the Vz of oxypaeoniflorin, the t1/2 of oxypaeoniflorin and the MRT of oxypaeoniflorin increased in the CIR rats versus the normal rats. Moreover, we found albiflorin and oxypaeoniflorin showed smaller AUC, longer MRT, larger Vz and larger CL than paeoniflorin both in CIR rats and normal rats. In conclusion, we used a validated method to determine the pharmacokinetic characteristics of three monoterpene glycosides in both CIR rats and normal rats simultaneously. These results demonstrated that there were meaningful differences among the pharmacokinetics of the three monoterpene glycosides in TPG either in normal rats or CIR rats. And the CIR model had influences on the in vivo process both of albiflorin and oxypaeoniflorin.