Investigation of a new core–shell particle column for ion-pair reversed-phase liquid chromatography analysis of oligonucleotides

• Oligonucleotide analysis by ion-pair reversed-phase liquid chromatography.
• Evaluation of a core–shell C18 column for improved separation of oligonucleotides.
• Long-term column stability test at pH 7 mobile phase and high column temperature.
• Evaluation of SunShell C18 column showed the column remained stable after more than 300 injections.

A new core–shell particle column showed excellent performance and durability for separation of short (∼21-mer) ribonucleic acid (RNA) oligonucleotides by ion-pair reversed-phase liquid chromatography (IP-RPLC). Previously investigated core–shell C18 columns showed excellent peak shapes and separations of closely eluting impurities by IP-RPLC. However, these columns showed only modest long-term stability at the neutral pH and elevated column temperatures of ≥60 °C, typically used for IP-RPLC analysis of oligonucleotides. The newly introduced SunShell C18 column provided separations comparable to the previously evaluated core–shell columns, but with significantly improved long-term column stability when operated at neutral pH and elevated column temperature.

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