Herb–drug interaction of Epimedium extract on the pharmacokinetic of dapoxetine in rats

•An HPLC–MS/MS method was developed for dapoxetine analysis in rat plasma.•Method validation with good linearity, accuracy, recovery and stability was developed.•The pharmacokinetic interaction between of Epimedium extract on the dapoxetine in rats was first reported.

The aim of study is to develop a high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method to investigate the pharmacokinetic interaction of Epimedium extract on the dapoxetine in rats. Experimental rats were divided into the following four parallel groups: (1) dapoxetine alone (10 mg/kg, i.v.); (2) oral administration of Epimedium extract (2 g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10 mg/kg, i.v.); (3) dapoxetine alone (10 mg/kg, p.o.); (4) oral administration of Epimedium extract (2 g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10 mg/kg, p.o.). The calibration curves of dapoxetine were acquired over a concentration ranges from 1 to 500 ng/mL with the R2 = 0.999. The mean matrix effects and extraction recoveries of dapoxetine at three different concentrations (1, 10, 500 ng/mL) ranged from 107.3 to 110.9% and from 25.5 to 28.2% respectively. The interday and intraday relative standard deviation were both <6% while the bias were both <14%. The pharmacokinetic results demonstrated that pretreated with/without Epimedium extract for three consecutive days did not significant alter the pharmacokinetics of dapoxetine in rats. The oral bioavailability of dapoxetine was about 75% in rats.