Evaluation of core–shell particle columns for ion-pair reversed-phase liquid chromatography analysis of oligonucleotides

An investigation into the use of core–shell particle columns for separation of short (∼21 base pairs) RNA oligonucleotides by ion-pair reversed-phase liquid chromatography (IP-RPLC) showed improved resolution for a number of test analytes relative to conventional (fully-porous) reversed-phase columns. The best resolutions were obtained using columns packed with smaller sub-2 μm core–shell particles.

► Oligonucleotide analysis by ion-pair reversed-phase liquid chromatography. ► Evaluation of different fused-core columns for oligonucleotide analysis. ► Fused-core columns provided improved separations of oligonucleotides. ► The sub-2 μm particle fused-core columns showed the best separations. ► Long term column stability was tested for fused-core columns.