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A novel LC-MS/MS method for the determination of favipiravir ribofuranosyl-5'-triphosphate (T-705-RTP) in human peripheral mononuclear cells.

Challenger, Elizabeth, Dilly-Penchala, Sujan, Hale, Colin, Fitzgerald, Richard, Reynolds, Helen, Chiong, Justin, Rowland, Tim, Fletcher, Tom, Khoo, Saye and Else, Laura (2024) 'A novel LC-MS/MS method for the determination of favipiravir ribofuranosyl-5'-triphosphate (T-705-RTP) in human peripheral mononuclear cells.'. Journal of Pharmaceutical and Biomedical Analysis, Vol 245, p. 116155.

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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.

Item Type: Article
Subjects: QU Biochemistry > Cells and Genetics > QU 350 Cellular structures
QU Biochemistry > QU 4 General works
QV Pharmacology > QV 38 Drug action.
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1016/j.jpba.2024.116155
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 07 May 2024 13:59
Last Modified: 07 May 2024 13:59
URI: https://archive.lstmed.ac.uk/id/eprint/24514

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