YMC Publishes IP-RP and AEX Oligo Method Guides

YMC Europe has published two Expert Tip guides on chromatographic method selection for therapeutic oligonucleotide analysis, covering both ion-pair reversed-phase (IP-RP) and anion exchange (AEX) chromatography. Released on 24 June 2026, the guides are aimed at scientists in pharmaceutical research, bioanalytics, quality control and analytical development, and provide structured guidance for developing robust, reproducible and MS-compatible methods across a widening range of oligonucleotide modalities.

The IP-RP guide covers what is widely regarded as the gold standard for separation and characterisation of therapeutic oligonucleotides, with method selection structured by sequence length. Short oligonucleotides need more hydrophobic ion-pair reagents for sufficient retention. Medium sequence lengths deliver robustness, precise peak shapes and strong LC-MS compatibility. Long oligonucleotides benefit from elevated temperatures and optimised ion-pair concentrations to reduce secondary structures and peak broadening. The guide also details how pore size, temperature and stationary phase affect selectivity, with dedicated attention to LC-MS-compatible TEA/HFIP systems and alternatives that avoid fluorinated alcohols.

The AEX guide takes the same length-based approach. Short sequences typically benefit more from RP or IP-RP; medium-length oligonucleotides sit in the optimal working range for AEX, with high length selectivity and precise resolution of n-1 and n+1 impurities; long oligonucleotides require elevated temperatures and denaturing conditions; and very long sequences see reduced resolution due to structural complexity. The document also addresses organic modifiers, salt gradients and denaturants, with particular focus on ammonium-based buffer systems for MS-compatible workflows and optimised conditions for phosphorothioate-modified oligonucleotides. Both guides support ASO, siRNA, sgRNA and mRNA analytical workflows.

The commercial signal here is category positioning rather than a single product launch. As therapeutic oligonucleotides mature from niche to mainstream pipeline modality across ASOs, siRNA and mRNA, method development expertise is becoming a genuine differentiator among chromatography suppliers. YMC’s technical publication strategy positions it alongside Thermo Fisher, Waters and Agilent as a serious voice in the analytical workflow conversation.

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