Simultaneous stereoselective analysis of venlafaxine and O-desmethylvenlafaxine enantiomers in clinical samples by capillary electrophoresis using charged cyclodextrins

Capillary electrophoresis (CE) was used for the simultaneous chiral determination of venlafaxine (Vx), a new antidepressant drug and its main active metabolite, O-desmethyl venlafaxine (ODV). Among the charged cyclodextrins (CD) tested, phosphated gamma-CD was the most appropriate. Resolution of Vx and ODV was obtained with 50 mM phosphate buffer (pH 2.5) containing 20 mg:ml of phosphated gamma-CD. After optimisation of the method (including robustness), validation was carried out. Vx and ODV concentrations, as well as the enantiomeric ratio, were investigated in clinical samples. Chiral determination of Vx and ODV was performed after a simple liquid-liquid extraction (LLE). In the tested concentration range (25-500 ng/ml), coefficients of correlation were superior to 0.996. Within-day and between-day accuracy and precision were determined at three different concentrations for each enantiomer. Analyses of clinical samples (n = 16) exhibited non-racemic ratios for Vx and ODV, which suggests a stereoselective metabolism in humans. (C) 2000 Elsevier Science B.V. All rights reserved.