Improved Oligonucleotide LC–MS Performance Through Inert Column Hardware And Alternative Separation Strategies

Oligonucleotide LC-MS is vulnerable to two persistent problems: analyte interactions with metal surfaces, and dependence on HFIP, a PFAS, for ion-pair reversed-phase work. This ASMS 2026 poster from Agilent Technologies scientists compares conventional ion-pair reversed-phase with ion-pair-free reversed-phase and HILIC, using the same stationary phases on stainless steel and inert column hardware. It also looks at how an inert flow path and polypropylene solvent bottles affect the data. Results span column equilibration, sample recovery, sodium adducts, and whether a 39-mer and 40-mer can still be resolved when ion-pair reagent is reduced.

Get a closer look at the comparison of what each separation mode gives up.