ArticleBioanalysis2026
A simple and highly sensitive LC-MS/MS bioanalytical method for phosphorodiamidate morpholino oligonucleotides in plasma.
Article in Bioanalysis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
backgroundLC-MS/MS is widely used for the quantification of phosphorodiamidate morpholino oligomers, but its low sensitivity is a problem. In addition, solid-phase extraction, a pretreatment method generally used for LC-MS/MS analysis, results in low recovery when applied to phosphorodiamidate morpholino oligomers. Therefore, a highly sensitive bioanalytical method for the determination of phosphorodiamidate morpholino oligomers using LC-MS/MS with improved pretreatment is desired.
resultsProtein precipitation was applied to LC-MS/MS analysis for viltolarsen, as a typical phosphorodiamidate morpholino oligomer, in plasma, and PPT with MeOH achieved high recoveries (>90%). Reversed-phase liquid chromatography (RPLC) with gradient elution improved ion suppression compared to hydrophilic interaction liquid chromatography. A combination of PPT and RPLC achieved higher sensitivity (lower limit of quantification, 1 ng/mL) than those of approved phosphorodiamidate morpholino oligomers (10 to 20 ng/mL in their clinical reviews), and the between-run accuracy and precision ranged from 97.1% to 109% and 2.56% to 10.5%, respectively. This method was also shown to be applicable to another phosphorodiamidate morpholino oligomer, ψM23D (+07-18).
conclusionA simple and highly sensitive bioanalytical method for the determination of viltolarsen was established by optimizing RPLC and PPT, and the method was successfully applied to a phosphorodiamidate morpholino oligomers with a different sequence.
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