A fully derivatized 4-chlorophenylcarbamate-β-cyclodextrin bonded chiral stationary phase for enhanced enantioseparation in HPLC

Abstract

This paper reports an effective approach for the fabrication of a per-4-chlorophenylcarbamate-β-cyclodextrin (β-CD) bonded chiral stationary phase (CPCDP) in high-performance liquid chromatography. The morphology and structure of the ligand and the chiral stationary phase (CSP) were characterized by scanning electron microscopy, transmission electron microscopy, solid state 13C nuclear magnetic resonance spectra, fourier transform infrared spectra, elemental analysis and thermogravimetric analysis. Because CPCDP was a kind of multimode enantioseparation materials, the enantioseparation of chiral compounds including twelve azole antifungal agents, five proton pump inhibitors and five dihydropyridine calcium antagonists were studied in both reversed-phase and normal-phase chromatography. All analytes were obtained enantiomeric separation. Especially, the resolution of azoles was excellent. The selectivity and resolution of voriconazole reached 15.41 and 16.80, which was an exciting achievement for the enantioseparations by β-CD based chiral stationary phases. Compared with the commercial 3,5-dimethylphenyl carbamate-β-CD based chiral stationary phase (DMP), enhanced enantioselectivities for all the above compounds (except ilaprazole) were obtained on CPCDP column, which indicated that the 4-chlorophenylcarbamate group was conducive to the chiral recognition. Chromatographic studies elucidated that enhancement of analyte–chiral substrate interactions were attributed to the inclusion complexation, π–π stacking interaction, hydrogen-bonding, dipole–dipole interaction and steric hindrance. For further study, we also prepared semi-preparative chromatographic columns to obtain a single enantiomer. In addition to excellent chromatographic performance, the prepared CD-based column is stable and much cheaper than commercial columns, which can reduce the cost of test and has a good application prospect in chiral drug analysis.