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.