Oligonucleotides are emerging new therapeutic entities and reliable selective analytical methods to determine their purity and related impurities are critical. Strong anion exchange (SAX) liquid chromatography (LC) methods are often used as an orthogonal method to well established ion-pairing reversed phase (IP-RP) methods, particularly for phosphorothioate oligonucleotides. However, the non-volatile eluents of SAX methods deem them not MS-compatible and are hindering direct peak purity analysis.

In this presentation, a novel 2D-LC-MS approach developed at Bachem will be described that allows the evaluation of peak purity by using SAX methods in combination with IP-RP and high-resolution MS.

Marion Fresch is Senior scientist in the QC Early Phase department at Bachem AG. She joined the company in 2021, specializing in HPLC method development, validations, forced degradation studies, release analytics, and stability testing for oligonucleotide NCE projects. Marion holds a PhD in analytical food chemistry from the university of Stuttgart where her interest in patient health grew as she was working on food allergen analysis.