Carboxylated cyclofructan 6 as a hydrolytically stable high efficiency stationary phase for hydrophilic interaction liquid chromatography and mixed mode separations

Abstract

Stationary phases composed of native cyclofructan 6 (CF6) and benzoic acid modified CF6 were synthesized and evaluated for hydrophilic interaction liquid chromatography (HILIC). The ligands were bonded onto 2.7 μm core–shell silica using multipoint attachment technology. These cyclofructan 6 based columns exhibited excellent hydrolytic stability and efficiency (205 000 N m⁻¹). The new column chemistry was compared for stability with core–shell silica (the starting material) using neutral, positive and a negatively charged probes. Additionally, the advantage of the use of a pre-saturating column in HILIC mode is shown. The HILIC selectivity chart shows that the benzoic acid modified cyclofructan-6 column shows strong hydrophilicity as well as cation exchange property. A variety of hydrophilic/ionizable compounds were examined, and based on the selectivity chart, it was found that the new column chemistry is different from 33 commercial columns. The benzoic acid CF6 column can simultaneously separate acidic, neutral and basic drugs and produced considerably different retention and selectivity patterns for various classes of compounds including nucleic acid bases, β-blockers, salicylic acid and its analogues. The newly developed column chemistry also shows a potential to work in the reverse phase mode.