Two Quantitative Assays for the Phosphorodiamidate Morpholino Oligomer (PMO) SRP-4045 in Mouse Plasma Using HPLC-MS/MS Coupled with Solid Phase Micro-Extraction

Phosphorodiamidate morpholino oligomers (PMO) are among the most advanced antisense therapeutics and a promising strategy for treating genetic disorders and infections. We have previously published two LC-MS/MS quantitative assays for positively charged PMOs (PMOplus) in human plasma and urine.1 SRP-4045 differs from PMOplus in that it is a neutral PMO containing 22 bases with a molecular weight >7500 Da, and is currently in development for patients with DuchenneMuscular Dystrophy. Here we report two sensitive, specific, and high-throughput LC-MS/MS assays for SRP-4045 in mouse plasma at both a low range (10.0-2,500 ng/mL) and a high range (2,000-500,000 ng/mL) in order to cover the wide range of expected sample concentrations.