Abstract

In this study, three small peptoids with different structures, named Sil-peptoids, were developed to improve the separation selectivity of zwitterion-exchange/reversed-phase mixed-mode chromatography stationary phases for multi-component complex drugs. Nonpolar, amphoteric, and alkaline drugs were used as test samples to demonstrate their retention behaviors in reversed-phase, ionic, and mixed-mode interactions. It was observed that different carboxyl anions in the small peptoids of the Sil-peptoids had vast differences in their stereo-selectivity. The stereo-selectivity and the influence of Sil-peptoids on the retention behavior of complex drugs and their interaction mechanism for the drug molecules were effectively evaluated through the combination of chromatographic analysis and molecular modeling. Finally, a mixture of drugs consisting of two polar and six non-polar drugs was used to obtain a separation effect with a resolution >1.5. Two other groups of polar antibiotics were used to verify the separation ability of the Sil-peptoids. The results indicated that the Sil-peptoids could separate multiple substances simultaneously. These novel stationary phases can be applied to the analysis of complex multi-component drugs.

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