Enantioseparation of venlafaxine and O-desmethylvenlafaxine by capillary electrophoresis with mixed cyclodextrins

Capillary electrophoresis (CE) has been successfully applied to the separation of the enantiomers of venlafaxine (Vx) and its main active metabolite, O-desmethylvenlafaxine (ODV), by use of a mixture of two cyclodextrins (CDs) added to the background electrolyte (BGE). The use of carboxymethylated ?-cyclodextrin (CMB) enabled the enantioseparation of both Vx and ODV, although separation of all four enantiomers was not achieved. Addition of a second cyclodextrin (?-CD) to the BGE resulted in the simultaneous resolution of the enantiomers of both compounds. In this system, ?-CD enabled discrimination between Vx and ODV whereas CMB enabled the enantioseparation. Resolution was strongly influenced by the ratio of the concentrations of the two complexing agents. Baseline resolution of Vx and ODV was achieved in an uncoated capillary. Addition of organic modifiers to the BGE had a substantial effect on the interaction of the analytes with the ?-CD.