Liquid chromatography tandem mass spectrometry method for the simultaneous stereoselective determination of venlafaxine and its major metabolite, O-desmethylvenlafaxine, in human plasma

A sensitive, accurate and highly stereoselective assay for the simultaneous determination of venlafaxine (VEN) and its equipotent metabolite, O-desmethyl venlafaxine (ODV), in human plasma was developed and validated. Analytes were simultaneously extracted from plasma using solid-phase extraction and detected by tandem mass spectrometry in positive ion mode with a turbo ion spray interface. Deuterium-labeled VEN and ODV were used as internal standards. Chromatographic separation was performed on a Chiral AGP column, using a time programmed gradient flow with a total run time of 16min. The method has a lower limit of quantitation of 0.60ng/mL. The assay was linear over a range 0.60300.00ng/mL for both the enantiomers of VEN and ODV, respectively, with coefficient of correlation>0.99. The extraction recoveries were >77.0% on an average for all the four analytes. The analytes were found stable in plasma through three freeze (15 degrees C) and thaw cycles and under storage at room temperature for 8h, and also in mobile phase at 10 degrees C for 54h. The method has shown good reproducibility, with intra- and inter-day variation coefficients<9%, for all the analytes, and has proved to be very reliable for analysis of VEN and its metabolite in clinical study samples. Copyright (c) 2012 John Wiley & Sons, Ltd.