Validation of chiral electrokinetic chromatography methods using highly sulfated cyclodextrins: Determination of enantiomeric purity of aromatase inhibitors

Electrokinetic chromatography methods for the enantiomeric resolution of four imidazole derivatives, potential aromatase inhibitors, were developed using highly Sulfated alpha-, highly Sulfated beta- and highly Sulfated gamma- CDs as chiral selectors at acidic pH. The optimization of the various operational parameters (nature and concentration of the CD, capillary length, buffer concentration, presence of organic modifier in the electrolyte, temperature and voltage) permits to obtain resolution factors superior to 3, for each racemic analyte, with migration times of the second enantiomers less than 6 minutes. The four optimal analytical methods were validated prior to the determination of the enantiomeric purity of the eight enantiomers previously isolated and analyzed by chiral HPLC.