System Optimization to Mitigate Signal Suppression While Autonomously Running Multiple LC/MS/MS Methods in for SiRNAs, Peptides and Small Molecules in Sequence

A major concern while performing analysis of siRNA therapeutics is the suppression effects of HFIP/TEA mobile phases on other LC/MS/MS methods. Negative ion pairing agents are needed for acceptable chromatography and can be useful for signal enhancement, however these are detrimental to other methods causing suppression on the instrument requiring significant down time for purging and cleaning of the system between assays. A successful workflow model was created to enable separate methods to be run in sequence on the same LC/MS/MS system by leveraging the capacity of a multi‐system LC on a single mass spectrometer. By utilizing multiplex capability, analysis of oligonucleotides incorporating the use of ion pairing agents can be included in a broad scope workflow on a single LC‐MS/MS system. Employing methods for switching autonomously, in concert with the analytical methods significantly increasing workflow capacity while minimize scientist hours freeing up time for method development or scientific oversight duties while the instrument performs the prescribed analysis.