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Characterization of oligonucleotides requires robust analytical instrumentation and methods as well as ease-of-use data analysis tools. Biocompatibility mitigates non-specific sample binding to flow path and it ensures the integrity of biomolecules and robustness of the system. In this study, two workflows, the Target Plus Impurities (TPI) and Sequence Confirmation workflows in Agilent MassHunter BioConfirm software, were carried out to characterize two oligonucleotide samples.