Enantioseparation of mandelic acid derivatives by high performance liquid chromatography with substituted β-cyclodextrin as chiral mobile phase additive and evaluation of inclusion complex formation

The enantioseparation of ten mandelic acid derivatives was performed by reverse phase high performance liquid chromatography with hydroxypropy1-beta-cyclodextrin (HP-beta-CD) or sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD) as chiral mobile phase additives, in which inclusion complex formations between cyclodextrins and enantiomers were evaluated. The effects of various factors such as the composition of mobile phase, concentration of cyclodextrins and column temperature on retention and enantioselectivity were studied. The peak resolutions and retention time of the enantiomers were strongly affected by the pH, the organic modifier and the type of beta-cyclodextrin in the mobile phase, while the concentration of buffer solution and temperature had a relatively low effect on resolutions. Enantioseparations were successfully achieved on a Shimpack CLC-ODS column (150 x 4.6 mm i.d., 5 mu m). The mobile phase was a mixture of acetonitrile and 0.10 mol L-1 of phosphate buffer at pH 2.68 containing 20 mmol L-1 of HP-beta-CD or SBE-beta-CD. Semi-preparative enantioseparation of about 10 mg of alpha-cyclohexylmandelic acid and alpha-cyclopentylmandelic acid were established individually. Cyclodextrin-enantiomer complex stoichiometries as well as binding constants were investigated. Results showed that stoichiometries for all the inclusion complex of cyclodextrin-enantiomers were 1:1. (C) 2014 Elsevier B.V. All rights reserved.