Sensitive LC-MS/MS Method for Cationic Ligand-Conjugated siRNA Therapeutics
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Posters
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September 12,2025
Posters Overview
To address the issue of low mass spectrometry response, ammonia solution was added to the plasma matrix to replace ammonium acetate buffer. The introduction of NH3·H2O leads to the deprotonation of amine groups on the ligand (NH2+ → -NH), reducing their positive charge and weakening their interaction with the matrix, thus preventing co-precipitation with the matrix. At the same time, the increase in OH results in the deprotonation of the siRNA phosphate backbone (-PO4H- → -PO42-), increasing its negative charge and enhancing hydrophilicity, which favors retention in the aqueous phase and improves extraction efficiency.
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