A Novel and Efficient LC-MS/MS Method for Quantitation of Polysarcosine in Mouse Plasma

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May 30,2026

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Assessing pSar's plasma stability is crucial to prevent off-target effects, enhancing efficacy and safety. Unlike traditional small molecules, pSar's multiple sarcosine (N-methylglycine) units linked by amide bonds result in variable molecular weight, complicating Q1 ion selection in liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Multiple positive charges contribute to non-specific binding (NSB) and severe peak tailing during sample extraction and analysis. We are the first to establish a rapid LC-MS/MS method for pSar with an average molecular weight of ~12,000 Da, overcoming all previous challenges to enable rapid assessment of pSar stability in mouse plasma.

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