Sulfobutylether-(hydroxypropyl-β-cyclodextrin) bonded silica as stationary phase for enhancing chiral separation in liquid chromatography.

The present study addresses the limited recognition modes and poor universality of conventional cyclodextrin-based chiral stationary phases (CSPs) by proposing a rational design strategy based on "functional group synergy" concept. Following this strategy, sulfobutylether-(hydroxypropyl-β-cyclodextrin), hereafter referred to as SBE-(HP-β-CD), was successfully synthesized and, for the first time, chemically bonded to silica matrix to fabricate a SBE-(HP-β-CD) CSP. Comprehensive evaluation demonstrated that this CSP exhibits superior chiral selectivity, higher column efficiency, and shorter retention times for a diverse set of 33 chiral analytes (including basic, acidic, and neutral compounds). Its overall separation performance was significantly better than that of single-functionalized reference CSPs (HP-β-CD CSP and SBE-β-CD CSP). Multimodal mechanism studies-integrating 1H NMR and thermodynamic analysis-provided direct evidence for a synergistic recognition effect arising from mixed functional groups. Furthermore, the CSP demonstrated excellent performance and good reproducibility in practical analysis of commercial antifungal ketoconazole ointment. This work not only presents a high-performance chiral stationary phase but also establishes a new paradigm for constructing multifunctional synergistic separation materials through rational molecular design.