Separation of five recently commercialized selective serotonin inhibitor antidepressants by capillary electrophoresis

The novel antidepressant reboxetine, a selective norepinephrine reuptake inhibitor, is increasingly used in the treatment of different forms of major depression. Reboxetine is a chiral compound, and is marketed as a racemic mixture of (R,R)- and (S,S)-reboxetine; however, the pharmacokinetic and toxicological profiles of the two enantiomers are rather different. For this reason, a simple capillary electrophoretic method for the separation of reboxetine enantiomers has been developed. Sulfobutyl ether-beta-cyclodextrin was chosen as the chiral selector, and several parameters, such as cyclodextrin and buffer concentration, buffer pH and capillary temperature were investigated in order to obtain good separation and acceptable run times. Using an uncoated, fusedsilica capillary (internal diameter 50 micron, total length 48.5 cm, effective length 40.0 cm) and a background electrolyte consisting of a pH 3.0, 100mM phosphate buffer containing 1.25 mM cyclodextrin, reboxetine enantiomers were baseline separated (resolution R= 4) with a voltage of 20 kV in less than 16 min. Since pure enantiomers of reboxetine were not available, they were obtained from the racemic powder by means of direct phase, high- performance liquid chromatography and their identity confirmed by circular dichroism spectra.