Abstract
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 (R2 =0.9994) in the range of 10-1000ng/mL. The quantification limit of venlafaxine in rat plasma was 10ng/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 Cmax (0.069mg/L) and AUC0→∞ (0.291mgh/L) in group B were statistically greater than that of Cmax (0.046mg/L) and AUC0→∞ (0.181mg·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.
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