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- Title
Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS-CoV-2/COVID-19 and Ebola virus disease.
- Authors
Avataneo, Valeria; Nicolò, Amedeo de; Cusato, Jessica; Antonucci, Miriam; Manca, Alessandra; Palermiti, Alice; Waitt, Catriona; Walimbwa, Stephen; Lamorde, Mohammed; Perri, Giovanni di; D'Avolio, Antonio; de Nicolò, Amedeo; di Perri, Giovanni
- Abstract
<bold>Background: </bold>Remdesivir has received significant attention for its potential application in the treatment of COVID-19, caused by SARS-CoV-2. Remdesivir has already been tested for Ebola virus disease treatment and found to have activity against SARS and MERS coronaviruses. The remdesivir core contains GS-441524, which interferes with RNA-dependent RNA polymerases alone. In non-human primates, following IV administration, remdesivir is rapidly distributed into PBMCs and converted within 2 h to the active nucleoside triphosphate form, while GS-441524 is detectable in plasma for up to 24 h. Nevertheless, remdesivir pharmacokinetics and pharmacodynamics in humans are still unexplored, highlighting the need for a precise analytical method for remdesivir and GS-441524 quantification.<bold>Objectives: </bold>The validation of a reliable UHPLC-MS/MS method for remdesivir and GS-441524 quantification in human plasma.<bold>Methods: </bold>Remdesivir and GS-441524 standards and quality controls were prepared in plasma from healthy donors. Sample preparation consisted of protein precipitation, followed by dilution and injection into the QSight 220 UHPLC-MS/MS system. Chromatographic separation was obtained through an Acquity HSS T3 1.8 μm, 2.1 × 50 mm column, with a gradient of water and acetonitrile with 0.05% formic acid. The method was validated using EMA and FDA guidelines.<bold>Results: </bold>Analyte stability has been evaluated and described in detail. The method successfully fulfilled the validation process and it was demonstrated that, when possible, sample thermal inactivation could be a good choice in order to improve biosafety.<bold>Conclusions: </bold>This method represents a useful tool for studying remdesivir and GS-441524 clinical pharmacokinetics, particularly during the current COVID-19 outbreak.
- Subjects
ADENOSINE triphosphate analysis; ALANINE analysis; ADENOSINE triphosphate; VIRAL pneumonia; RESEARCH; HIGH performance liquid chromatography; EBOLA virus disease; RESEARCH methodology; COVID-19; EVALUATION research; MEDICAL cooperation; ALANINE; COMPARATIVE studies; MASS spectrometry; EPIDEMICS; ADENOSINE monophosphate
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2020, Vol 75, Issue 7, p1772
- ISSN
0305-7453
- Publication type
Journal Article
- DOI
10.1093/jac/dkaa152