LC-MS Bioanalytical Quantification of a GalNAc-siRNA Conjugate Oligonucleotide Using Semi-Automated Solid Phase Extraction

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Mary Trudeau, Kathryn Brennan
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This application highlights the successful SPE extraction and LC-MS/MS quantification of a GalNAc-siRNA conjugated oligonucleotide from neat solution and post-spiked extracted plasma and urine. Using Pipette+ and Otto SPEcialist simplified and streamlined sample preparation and extraction procedures, maximizing productivity, reducing errors, and ensuring overall analytical performance of the method. The ACQUITY Premier LC and Oligonucleotide BEH C18 Column, specifically designed to mitigate adsorption of metal sensitive analytes, ensured consistently high levels of oligonucleotide recovery. The analytical sensitivity of this method achieved a LOD of 1 ng/mL from extracted plasma and urine for a GalNAc-siRNA conjugated oligonucleotide

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