An octyl-quaternary ammonium (Sil-C8-QA)-modified silica stationary phase was prepared by a two-step vapor deposition method which can substantially reduce the consumption of toxic organic solvents. The structure of the dual-functional ligands stationary phase was characterized by Fourier transform infrared spectroscopy and solid-state 13C CP/MAS NMR. Following elemental analysis, the surface density of octyl and quaternary ammonium bonding amount is 2.13 µmol m−2 and 0.77 µmol m−2, respectively. The efficiency and selectivity of the two-ligand phases were compared with two sole functional ligand phases: quaternary ammonium (Sil-QA)- and octyl-modified silica (Sil-C8). Chromatographic evaluation demonstrated a mixed-mode reversed-phase/anion-exchange retention property on the Sil-C8-QA column. The retention behavior of a homologous series of alkylbenzoic acids on the synthesized phase was systematically studied by changing the pH, ionic, and solvent strength of the mobile phase. A well-established mixed-model mechanism was confirmed. The Sil-C8-QA phase can predominantly enhance the retention of acidic drugs and improve their selectivity. It was also successfully applied to the simultaneous separation and determination of three kinds of compound preparations with large differences in component polarity.
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