Simultaneous separation of atenolol enantiomers and its acid/alkaline degradation impurities on mixed-mode chiral ligand exchange stationary phases.

Simultaneous separation of the enantiomer and impurities is a huge challenge for the quality control of the chiral drug. In this work, mixed-mode chiral ligand exchange stationary phases (CSPs) modified by octyl and sulfhydryl ligands were prepared by vapor deposition and click chemistry methods. Qualitative and quantitative determination of the prepared CSPs were achieved by Fourier transform infrared spectroscopy, solid-state 13 C CP/MAS NMR, and elemental analysis. The chiral resolution of CSPs was investigated through a comprehensively chromatographic evaluation of various racemates. Besides, the thermodynamic experiment was carried out to elucidate the contribution of hydrophobic ligand to the improvement of chiral recognition and selectivity. Atenolol and its degradation products were analyzed on the synthesized CSPs and compared with the commercial chiral column. A good separation of atenolol enantiomers from its acid and alkaline degradation impurities was simultaneously achieved on the C8 /L-Hypro CSP. This new CSP is expected to have more applications in the quality control of other chiral drugs.