Abstract
The hydrophilic interaction liquid chromatography behavior of a novel trimodal stationary phase with reversed‐phase/cation‐exchange/anion‐exchange characteristics was studied. This material is based on nanopolymer silica hybrid technology and provides reversed‐phase, strong cation‐exchange and weak anion‐exchange properties at the same time. It is constructed with high‐purity porous spherical silica particles coated with charged organic polymer nano‐beads (d~p~ ∼100 nm). The inner‐pore area of the silica gel is covalently modified with an organic layer that provides both reversed‐phase and weak anion‐exchange properties. The outer surface is modified with strong cation‐exchange functionality. This chemistry ensures distinctive spatial separation of the anion‐exchange and cation‐exchange regions, which allows both retention mechanisms to function simultaneously and provides more flexibility in selectivity control. The new phase exhibits hydrophilic interaction liquid chromatography characteristics: at high acetonitrile levels, the retention for charged analytes is governed by an ion‐exchange process, accompanied by hydrophilic interaction (partitioning mechanism). This feature provides good flexibility in pharmaceutical method development such as simultaneous separation of hydrophilic drug molecule and its counterions (e.g. penicillin G potassium salt).