Observations from a decade of oligonucleotide bioanalysis by LC–MS

Ewles M, Ledvina AR, Powers B & Thomas CE | Bioanalysis, 16(12), 6–629, (2024) Keywords: • bioanalysis • chromatographic • HRMS • LC–MS • oligonucleotide • perspective • siRNA • triple quadrupole There is a growing need for efficient bioanalysis of oligonucleotide therapeutics. This broad class of molecules presents numerous challenges relative to traditional small molecule therapeutics. Methodologies including ligand-binding assays or polymerase chain reaction may be fit-for-purpose in many instances, but liquid chromatography coupled to mass spectrometry (LC–MS) often delivers the best balance of sensitivity and selectivity. Over the last decade, we have engaged with many such molecules and...