Applications of Highly Sulfated Cyclodextrins for Enantiomeric Separation by Capillary Electrophoresis

Abstract Separation of enantiomeric pairs of compounds by capillary electrophoresis (CE) was performed using highly sulfated α‐, β‐ and γ‐cyclodextrins (HS‐CDs). CE analysis of the HS‐CDs using indirect absorbance detection showed that the new class of chiral selectors has substantially higher degrees of sulfation and narrower heterogeneity than those used in previous reports. Elemental analyses showed that the average number of sulfate groups per cyclodextrin was 11, 12, and 13, for HS‐α, β and γCD, respectively. Our earlier 13C NMR data of HS‐CDs were consistent with the structural assignment of complete sulfation at the C‐6 primary hydroxyl groups, greater than 70% sulfation at the C‐2 secondary hydroxyls and absence of substitution at the C‐3 hydroxyls. CE‐based chiral separations were performed using a generalized procedure with phosphate buffer (pH 2.5) containing 5% (w/v) HS‐CD in a 50 μm I.D. × 31 cm (total length) fused silica capillary. Quantitation of enantiomeric impurity of less than 1% was demonstrated for pseudoephedrine and phenylpropanolamine. The HS‐α, β and γCD complement each other by exhibiting different chiral selectivity. The combination of HS‐α, β and γCD resolved more than 140 chiral compounds of neutral, acidic and basic drugs with very different structural features. The HS‐CDs were synthesized under conditions of controlled sulfation to produce chiral reagents with consistent composition, making them excellent chiral selectors for capillary electrophoretic analysis of enantiomeric impurities.