1. A novel LC-MS/MS method for the determination of favipiravir ribofuranosyl-5'-triphosphate (T-705-RTP) in human peripheral mononuclear cells.
- Author
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Challenger E, Dilly-Penchala S, Hale C, Fitzgerald R, Reynolds H, Chiong J, Rowland T, Fletcher T, Khoo S, and Else L
- Subjects
- Humans, COVID-19, COVID-19 Drug Treatment, Liquid Chromatography-Mass Spectrometry, Reproducibility of Results, SARS-CoV-2 drug effects, Solid Phase Extraction methods, Tandem Mass Spectrometry methods, Amides chemistry, Antiviral Agents pharmacokinetics, Antiviral Agents analysis, Leukocytes, Mononuclear metabolism, Pyrazines pharmacokinetics, Pyrazines analysis
- Abstract
Favipiravir is a broad-spectrum antiviral that is metabolised intracellularly into the active form, favipiravir ribofuranosyl-5'-triphosphate (F-RTP). Measurement of the intracellular concentration of F-RTP in mononuclear cells is a crucial step to characterising the pharmacokinetics of F-RTP and to enable more appropriate dose selection for the treatment of COVID-19 and emerging infectious diseases. The described method was validated over the range 24 - 2280 pmol/sample. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and lysed using methanol-water (70:30, v/v) before cellular components were precipitated with acetonitrile and the supernatant further cleaned by weak anion exchange solid phase extraction. The method was found to be both precise and accurate and was successfully utilised to analyse F-RTP concentrations in patient samples collected as part of the AGILE CST-6 clinical trial., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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