Wide pH range enantioseparation of cyclodextrin silica-based hybrid spheres for high performance liquid chromatography

Abstract pH plays an important role in the enantiomeric separation process by changing the polarity of the mobile phase and the conformation and ionization state of the enantiomers. Herein, β-cyclodextrin-silica hybrid spheres with n-propyl groups as hydrophobic linkers and ethyl-silica as a support were prepared using a one-pot approach, and then the hydroxyl group was further modified with 3,5-dimethylphenyl isocyanate. The new β-cyclodextrin-silica hybrid chiral stationary phase (CD-HCSP) was prepared and characterized using techniques including scanning electron microscopy and transmission electron microscopy. The enantioseparation properties of CD-HCSP were evaluated with different solvents over a wide pH range (1–10) in reversed phase. 14 enantiomers were successfully resolved, and favorable chiral resolution and high stability was demonstrated for multiple types of enantiomer under different pH conditions. Compared with commercial columns, CD-HCSP showed better chiral resolution and, more importantly, could be used for chiral resolution over a wide pH range. This work combines the high pH tolerance of the hybrid material and excellent chiral recognition of cyclodextrin for enantioseparation of chiral drugs, which could lead to the development of a new type of chiral separation material.