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Four chiral basic analytes, namely methadone, fluoxetine, venlafaxine, and tramadol, were selected as model compounds for investigating their stereoselective separation with highly sulfated gamma-cyclodextrin (HS gamma-CD) by capillary electrophoresis (CE)-UV and CE-mass spectrometry (MS). At high concentration of chiral selector, the preferentially bonded enantiomer migrated faster in the anodic mode to the detector and high resolutions were obtained for all analytes. In the cathodic mode, at lower highly sulphated cyclodextrin (HS-CD) concentration, basic compounds could be detected, with the weakly bonded enantiomer migrating first (enantiomeric migration order inversion). It was also then possible, at intermediate HS-CD concentration, that only one enantiomer migrated to the detector as cation while the other enantiomer complexed with the CD was negatively charged and presented an opposite mobility. The latter never reached the detector achieving a perfect enantiomeric selectivity. Infinite chiral resolutions were thus achieved by CE-UV as well as by CE-electrospray ionisation (ESI)-MS where concentrations of HS-CD were adapted according to the negative contribution of the nebulization gas pressure of the interface.

The simultaneous enantioseparation of selected anesthetic drugs was studied by capillary electrophoresis (CE) in presence of three different negatively charged cyclodextrins (CDs). Among the chiral selectors tested, namely carboxymethyl, sulfobutyl ether and sulfated-beta-CD, the latter appeared to be the most effective to achieve the enantiomeric resolution of the investigated compounds. Beside CD type, resolution was greatly influenced by the buffer pH, the molecular structure of the anesthetic compounds, CD concentration and temperature. The optimum electrophoretic conditions for the stereoselective analysis of the studied anesthetics were obtained with a poly(vinyl alcohol) coated capillary (48.5 cm total length x 50 microm I.D.), a 50 mM Tris-phosphate buffer at pH 2.5 containing 6 mg ml(-1) of sulfated-beta-CD, an applied voltage of 30 kV and a temperature of 30 degrees C. Under these optimized conditions, four drugs, namely bupivacaine, mepivacaine, ketamine and prilocaine, were simultaneously enantioresolved in less than 12 min. Furthermore, the method was applied to the stereoselective analysis of mepivacaine in a pharmaceutical preparation. Finally, the method was on-line coupled to electrospray ionization mass spectrometry using the counter current partial-filling technique.

A capillary zone electrophoresis (CZE) method, with sulfated beta-CD as chiral selector, was optimized by means of an experimental design for the enantioseparation of atropine. In this study, a central composite design was used and the following factors were varied simultaneously: buffer concentration, buffer pH and sulfated beta-CD concentration. The resolutions between littorine and its positional isomer ((-)-hyoscyamine) and between atropine enantiomers, as well as the separation time and generated current were established as responses. A model was obtained for each response by linear multiple regression of a second-degree mathematical expression. The most favorable conditions were determined by maximizing the resolution between atropine enantiomers and by setting the other responses at threshold values. Successful results were obtained with a 55 mM phosphate buffer at pH 7 in the presence of 2.9 mM sulfated-beta-CD at 20 degrees C and 20 kV. Under these optimized conditions, a baseline separation of littorine and atropine enantiomers was achieved in less than 5 min. Finally, the method allowed the enantiomeric separation of atropine in a pharmaceutical formulation and was also found to be suitable for the enantiomeric purity evaluation of (-)-hyoscyamine in plant extracts, in relation with the extraction procedure. It was demonstrated that supercritical fluid extraction induced less racemization than classical liquid-solid extraction procedures.

A capillary zone electrophoresis method was developed for the enantioseparation of celiprolol enantiomers, using a sulfated beta-cyclodextrin (beta-CD) as a chiral selector. The use of a coated capillary was necessary to achieve stable and reproducible enantioseparations. A central composite design was applied to optimize the method and four parameters were selected for this study: the buffer pH, the buffer concentration, the sulfated beta-CD concentration and the temperature. Resolution between celiprolol enantiomers as well as analysis time and generated current were established as responses. For each response, a model was obtained by a second-degree mathematical expression. From the models, the most favorable conditions were determined by optimizing the resolution between celiprolol enantiomers and by setting the two other responses at threshold values. Response surfaces were also used to assess the robustness of the analytical method around the optimal region. Successful results were obtained with a 52 mM acetate buffer at pH 4.0 in the presence of 3.0 mM sulfated beta-CD at a temperature of 19.5 degrees C. Under these optimized conditions, baseline separation of the celiprolol enantiomers was achieved in less than 10 min. The method showed good validation data in terms of precision, accuracy and linearity, and was found to be suitable in determining celiprolol enantiomers in pharmaceutical preparations and in biological fluids.