Fully Automated Candidate Creation Workflow for Intact Mass Mapping of Oligonucleotide Therapeutics

May 5, 2025

Given their molecular diversity, structural complexity, and challenging chemical synthesis, oligonucleotide therapeutics demand rigorous characterization and quality control. With Mass Spectrometry (MS) rapidly becoming the analytical platform of choice, a flexible MS data analysis workflow is required to manage the vast complexity of oligonucleotide variants, synthesis side products, impurities, and metabolites. Here, we present a fully automated oligonucleotide candidate creation workflow for intact mass mapping that offers unparalleled flexibility and analysis control by enabling users to define individual building blocks, such as linkers, bases, and sugars, and create customized nucleotide candidates for clips, modifications, insertions, and deletions. This eliminates manual work and leads to the generation of comprehensive search libraries to be used for the identification and monitoring of oligonucleotide candidates.