A Novel Enantioselective Chitosan-Based Stationary Phase Prepared by Molecular Imprinting of a Racemic Template

Chitosan is a chiral polyglucosamine polysaccharide that selectively binds to S-enantiomer of ketorolac rather than R-enantiomer. In this paper, a novel chiral stationary phase was prepared by molecular imprinting of chitosan using racemic ketorolac as a template. This imprinting process resulted in a high enantioselectivity (59.66% ee and enantioselectivity coefficient of 2.6) as evaluated by the batch rebinding study. The prepared stationary phase enabled chiral resolution of racemic ketorolac when packed into a solid-phase extraction cartridge. Moreover, promising results were obtained when an HPLC column packed with the proposed stationary phase was tested for chiral separation. The selectivity factor (α) was calculated to be 5.3 indicating the enantioselectivity of the prepared stationary phase. The chromatographic resolution trials revealed a mixed hydrophilic interaction liquid chromatography (HILIC) and reversed-phase (RP) separation modes in addition to the imprinted cavities. These results showed that racemic compounds could be cheaper and more available templates for imprinting of enantioselective polymers for chiral stationary phases.