Development and validation of a gas chromatographic–mass spectrometric method for quantitative determination of perphenazine in rabbit plasma after sublingual administration

Perphenazine is a phenothiazine-type antipsychotic that is a potential candidate for sublingual administration due to its extensive first-pass metabolism. In this study, a gas chromatographic–mass spectrometric method was developed for quantification of perphenazine in rabbit plasma after sublingual administration. The plasma samples were purified by mixed-mode solid phase extraction with good recovery (>83%). The method was linear (r2 > 0.99) over a range of 2–64 ng/ml, with a lower limit of quantification of 2 ng/ml. The accuracy was 100 ± 4%, and the within-day and between-day precisions were <6.8% R.S.D. and <14% R.S.D., respectively. Perphenazine was stable in stock solutions and plasma. The method was successfully applied for analysing perphenazine in plasma after sublingual administration to rabbits.