Enantiomeric Resolution of Pharmaceuticals in Capillary Electrophoresis Using Charged and Modified Cyclodextrins: Migration Order, Modeling, and Chiral Resolution Mechanism

The enantiomers of acenocoumarin, coumatetralyl, naproxen, and warfarin were resolved using β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, and heptakis(2,3-di-O-methyl-6-sulfo)-β-cyclodextrin with MES buffer with 0.1% (m/v) hydroxymethyl cellulose as background electrolyte. The migration times and theoretical plates number for R- and S-enantiomers were in the range of 5.08-61.70 and 5.21-65.29 min and 4515-658 045 and 6160-678 976. The values of the selectivity coefficients and resolution factors were 1.02-1.07 and 0.79-4.43, respectively. The enantiomers migration reversal order was determined for the reported racemates. Using a coumatetralyl as an example, the chiral recognition mechanism was determined. The simulation study confirmed the binding energy of R- and S-enantiomers of coumatetralyl as -6.40 and -6.10 kcal/mol; leading R-enantiomer migration first followed by S-enantiomers. The reported methods are useful for the enantiomer ratio of the reported racemates in any unknown samples.