Rapid Solid-Phase Extraction Coupled with GC-MS Method for the Determination of Venlafaxine in Rat Plasma: Application to the Drug-Drug Pharmacokinetic Interaction Study of Venlafaxine Combined with Fluoxetine.

A rapid and sensitive gas chromatography with mass spectrometry method for the determination of venlafaxine in rat plasma has been developed and applied to a drug-drug interaction study of fluoxetine on pharmacokinetics of venlafaxine in rats. Rat plasma was spiked with 2% aqueous ammonia before subjected to preactivated C18 solid-phase extraction columns and eluted with methanol. No endogenous interferences were observed under optimal condition. The calibration curve was linear (R-2 = 0.9994) in the range of 10-1000 ng/mL. The quantification limit of venlafaxine in rat plasma was 10 ng/mL. The accuracy was in the range of 85-110%, and the extraction recovery was no less than 50%. Both the intra-and interday precision were 5.0-10.7%. The concentration-time curve showed that plasma concentrations of the coadministration group (group B) were higher than that of single dose group (group A). Both values of C-max (0.069 mg/L) and AUC(0 ->infinity) (0.291 mg h/L) in group B were statistically greater than that of C-max (0.046 mg/L) and AUC(0 ->infinity) (0.181 mg.h/L) in group A (P < 0.05). The results indicated that a significant effect of fluoxetine was shown on the pharmacokinetics of venlafaxine, suggesting that drug-drug interactions are of concern for the treatment of depression with the combined use of venlafaxine and fluoxetine.