Therapeutic oligonucleotides offer promising treatments—typically by antisense interactions or siRNA-mediated effects—for a wide range of medical conditions that cannot be effectively treated by small-molecule or protein therapeutics. Current mass spectrometry (MS) based identification (ID) testing is straightforward, generally only requiring a m/z measurement for the target molecule. However, to facilitate deployment in regulated manufacturing environments, a range of system suitability tests (SSTs)—which can create labor-intensive manual calculations that may be subject to errors—need to be performed. Liquid chromatography (LC) data with both MS and UV detection was processed and analyzed using Genedata Expressionist software (Genedata AG, Basel). An automated data processing workflow was developed to identify the therapeutic oligonucleotides using the observed m/z value, while SST criteria (e.g., retention time, peak area, and sample purity) were verified using UV-based measurements. The entire workflow was fully automated, which not only dramatically accelerated data analysis in comparison to manual measurements, but also significantly decreased the risk of errors. The approach taken in Genedata Expressionist ensured that all measurements were done automatically, free from human input, and all within the same data platform; thereby facilitating the implementation of the assay in regulated environments.