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

Abstract

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 C 8 /L-Hypro CSP. This new CSP is expected to have more applications in the quality control of other chiral drugs.

Use of Commercial Mixed-Mode Stationary Phases and Sorbents in the High-Performance Liquid Chromatography Analysis and Solid-Phase Extraction of Ionized and Hydrophilic Bioactive Compounds

“…Novel mixed-mode stationary phases bearing chiral moieties have been reported. For example, a mixed-mode chiral stationary phase containing chiral hydroxyproline and octyl groups bound to silica particles enabled the effective separation of the enantiomers of a β-blocker, atenolol (Figure 5), within 20 min using methanol:0.2 mM copper sulfate (pH 4.6) (10:90) as the mobile phase [18]. Furthermore, we performed precolumn diastereomer derivatization followed by separation using a mixed-mode stationary-phase column (Scherzo ® SS-C18) to analyze amino acids in commercial garlic foodstuffs [17].…”

“…Novel mixed-mode stationary phases bearing chiral moieties have been reported. For example, a mixed-mode chiral stationary phase containing chiral hydroxyproline and octyl groups bound to silica particles enabled the effective separation of the enantiomers of a β-blocker, atenolol (Figure 5), within 20 min using methanol:0.2 mM copper sulfate (pH 4.6) (10:90) as the mobile phase [18].…”