Liquid chromatography–mass spectrometry method for the determination of venlafaxine in human plasma and application to a pharmacokinetic study

A sensitive and selective liquid chromatographic–mass spectrometric (LC–MS) method for the determination of venlafaxine in human plasma has been developed. Samples were prepared using liquid–liquid extraction and analyzed on a C 18 column interfaced with a triple quadrupole mass spectrometer. Positive electrospray ionization was employed as the ionization source. The mobile phase was methanol–water containing 10 mmol/L ammonium acetate, pH 7.9 adjusted with aqueous ammonia (80:20, v/v) at the flow rate of 1.0 mL/min. The analyte and internal standard clozapine were both detected by use of selected ion monitoring mode. The method was linear in the concentration range of 1.0–200.0 ng/mL. The lower limit of quantification (LLOQ) was 1.0 ng/mL. The intra‐ and inter‐day relative standard deviation across three validation runs over the entire concentration range was less than 10.1%. The accuracy determined at three concentrations (5.0, 50.0 and 150.0 ng/mL for venlafaxine) was within ±10.0% in terms of relative error (RE). The method was successfully applied for the evaluation of pharmacokinetic profiles of venlafaxine capsule in 20 healthy volunteers. The results show AUC, T max , C max and T 1/2 between the testing formulation and reference formulation have no significant difference ( p > 0.05). Relative bioavailability was 103.4 ± 14.1%. Copyright © 2007 John Wiley & Sons, Ltd.