[Chromatographic behavior of basic drugs on thioether-embedded benzenesulfonate silica stationary phases]

Mixed-mode chromatography (MMC) has pronounced advantages in the separation and analysis of complex samples. Compared with single-mode chromatography, the solute retention in MMC is controlled by multiple interactions, and the retention mechanism is more complicated. In this work, two thioether-embedded benzenesulfonate silica single-ligand and mixed-ligand stationary phases were prepared by thiol-ene click chemistry. The retention mechanisms of four basic drugs were investigated under various mobile phase compositions (pH, ionic and solvent strength). The results showed that both stationary phases have the mixed retention mechanism of the reverse phase and ion exchange. By changing the salt concentration of the mobile phase, the relationship between the retention factors of basic drugs and the reciprocal of ionic strength were investigated. The results indicate that a three-interaction-form model, containing reversed-phase, pure ion-exchange, and hydrophobically assisted ion-exchange interaction, is more suitable for the mechanism study of MMC. The quantitative results demonstrate that ion-exchange interaction composed of pure ion-exchange and hydrophobically assisted ion-exchange interaction is dominated on two phases. The relative contribution of each mechanism was varied with the solute, mobile phase composition, and ligand type and ratio. In addition, the hydrophobically assisted ion-exchange interaction had a significant impact on the solute retention and separation selectivity. These fundamental studies on the MMC retention mechanism are of great theoretical significance for the novel stationary phase design and the optimization of complex sample separation.