Oligonucleotide therapeutics have emerged in recent years as a powerful alternative to small molecule and protein therapeutics. Manufacturing and quality control of oligonucleotide therapeutics requires highly selective and sensitive LC-MS methods. This presentation will highlight two recently introduced software applications: one used for purity analysis and rapid intact mass confirmation of oligonucleotide impurities, the second one for fast data interpretation of complex oligonucleotide fragmentation spectra. These two applications are embedded in an automated, compliance-ready LC-MS workflow designed for analysis of synthetic oligonucleotides and their impurities.