Quantitative HPLC-MS/MS determination of Nuc, the active metabolite of remdesivir, and its pharmacokinetics in rat
- 24 July 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Analytical and Bioanalytical Chemistry
- Vol. 413 (23), 5811-5820
- https://doi.org/10.1007/s00216-021-03561-8
Abstract
Remdesivir is a nucleotide analog prodrug that has received much attention since the outbreak of the COVID-19 pandemic in December 2019. GS-441524 (Nuc) is the active metabolite of remdesivir and plays a pivotal role in the clinical treatment of COVID-19. Here, a robust HPLC-MS/MS method was developed to determine Nuc concentrations in rat plasma samples after a one-step protein precipitation process. Chromatographic separation was accomplished on Waters XBrige C18 column (50 × 2.1 mm, 3.5 μm) under gradient elution conditions. Multiple reaction monitoring transitions in electrospray positive ion mode were m/z 292.2 → 163.2 for Nuc and 237.1 → 194.1 for the internal standard (carbamazepine). The quantitative analysis method was fully validated in line with the United States Food and Drug Administration guidelines. The linearity, accuracy and precision, matrix effect, recovery, and stability results met the requirements of the guidelines. Uncertainty of measurement and incurred sample reanalysis were analyzed to further ensure the robustness and reproducibility of the method. This optimized method was successfully applied in a rat pharmacokinetics study of remdesivir (intravenously administration, 5 mg kg−1). The method can act as a basis for further pharmacokinetic and clinical efficacy investigations in patients with COVID-19. Graphical abstractKeywords
Funding Information
- Scientific Research Foundation of Capital Medical University (PYZ20022)
- Beijing Municipal Administration of Hospitals’ Youth Program (QML20180305)
- Beijing Municipal Natural Science Foundation (7164262)
- National Natural Science Foundation of China (81703611)
This publication has 19 references indexed in Scilit:
- Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infectionProceedings of the National Academy of Sciences of the United States of America, 2020
- Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitroCell Research, 2020
- A selective and robust UPLC-MS/MS method for the simultaneous quantitative determination of anlotinib, ceritinib and ibrutinib in rat plasma and its application to a pharmacokinetic studyThe Analyst, 2019
- Optimized UPLC–MS/MS method for the quantitation of olanzapine in human plasma: application to a bioequivalence studyBioanalysis, 2019
- Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymeraseAntiviral Research, 2019
- Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronavirusesScience Translational Medicine, 2017
- Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeysNature, 2016
- Development and validation of an ultrafiltration-UPLC-MS/MS method for rapid quantification of unbound docetaxel in human plasmaJournal of Chromatography B, 2014
- Measurement uncertaintyJournal of Chromatography A, 2007
- Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasmaBiochemical Pharmacology, 2005