VALIDATION OF ENANTIOMERIC SEPARATIONS BY MICELLAR ELECTROKINETIC CAPILLARY CHROMATOGRAPHY USING SYNTHETIC CHIRAL SURFACTANTS

摘要

The first report on the feasibility of method validation for the separation of enantiomeric mixtures by chiral micelle electrokinetic capillary chromatography is described. Method validation data elements were investigated according to U.S. Pharmacopeia protocol and are reported for the separation of ephedrine enantiomers using the synthetic chiral surfactants (S)- and (R)-N-dodecoxycarbonylvaline as buffer additives. Excellent linearity from 1-150% of the target concentration was obtained. A 1.0% limit of quantitation for an enantiomeric impurity with acceptable precision is shown. Method robustness and ruggedness is also presented. Migration order reversal was used for the determination of a trace enantiomeric impurity, and to identify the enantiomeric compound in a multiple active ingredient formulation. The capability to reverse migration order is shown to be a valuable tool to satisfy the U.S. Pharmacopeia specificity requirement as well as improving detection and quantitation limits.