Design, Fabrication, and Application of a Chiral Cyclodextrin Stationary Phase for Enantiomeric Separation and Analysis

Cyclodextrin-based chiral stationary phases (CSPs) have attracted considerable interest in the field of enantiomeric separation due to their chiral recognition properties. However, the design and preparation of cyclodextrin-based CSPs with satisfactory application prospects are necessary for further exploration. Herein, we report an effective method for fabricating β-cyclodextrin-derived CSP by chemical bonding of 3,5-dimethylphenylcarbamate-mono-6-ethylenediamine-β-cyclodextrin (i.e., DMPCCB) onto silica microspheres via the diamine linker. After structure characterization, the performances in enantiomeric separation were assessed using chiral drugs, including proton pump inhibitors, flavanones, and dihydropyridine calcium channel blockers, under the reversed-phase mode through high-performance liquid chromatography (HPLC). As a result, DMPCCB chirally recognized the tested analytes, where 11 out of 15 analytes were baseline enantioseparated. The promising enantioselectivity was attributed to the introduction of methyl groups on DMPCCB, resulting in flexible host-guest interactions that enhanced chiral recognition for the tested analytes. Under this background, a novel enantioselective HPLC-tandem mass spectrometry method based on DMPCCB chiral column was developed and validated for the determination of naringenin enantiomers in rat plasma, and successfully applied to a pharmacokinetics study. Findings showed a significant enantioselective absorption and elimination for naringenin enantiomers in both normal and acute alcoholic liver injury rats. This work provided a new idea for the preparation of cyclodextrin-based CSPs, making it a promising application in the analysis of chiral drugs.