Comprehending COVID-19: LC-MS/MS Analysis of Small Molecule Anti-Viral and Anti-Inflammatory Drugs in Plasma in Clinical Research

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Dominic Foley Lisa J. Calton David Morrissey
Waters Corporation
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A simple and rapid LC-MS/MS method has been developed for the analysis of anti-viral and anti-inflammatory drugs in plasma for clinical research using the ACQUITY UPLC I-Class/Xevo TQ-S micro IVD System. 

The method uses a simple protein precipitation to extract the drugs from plasma and chromatography with a CORTECS T3 Column to enable selective and rapid separation of the drugs in the extracted sample. Analytical sensitivity, linearity, precision, and accuracy are excellent with reproducible extraction efficiency and matrix effects.

Clinical research into the impact of these drugs and their metabolites on SARS-CoV-2 is still ongoing. Phosphorylated metabolites of the RNA polymerase inhibitors haven’t been evaluated here and they may be of additional interest, with nucleoside triphosphate of remdesivir representing the predominant metabolite in Peripheral Blood Mononuclear Cells (PBMCs).3 Phosphorylated molecules bind to metals and represent an analytical challenge for robust and reproducible quantification in LC-MS/MS. Chelator additives or the use of high performance surface (HPS) technologies can help bridge the gap in providing a method for robust quantification of phosphorylated molecules in future studies using LC-MS/MS.

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