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.