Evidence map›Paper›PMID 32361744›Full record

ArticleThe Journal of antimicrobial chemotherapy2020

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.

Valeria Avataneo, Amedeo de Nicolò, Jessica Cusato, Miriam Antonucci, Alessandra Manca, Alice Palermiti, Catriona Waitt, Stephen Walimbwa, Mohammed Lamorde, Giovanni di Perri and 1 more

Open access · bronzeAbstract readValidation Study
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.1field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 105 citations in OpenAlex.

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  8. AssessingThe veterinary quarterly · 2024
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  12. Deuremidevir and Simnotrelvir-Ritonavir for the Treatment of COVID-19.ACS pharmacology & translational science · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Valeria AvataneoLaboratory of Clinical Pharmacology and Pharmacogenetics, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin, Turin, Italy.
Amedeo de NicolòLaboratory of Clinical Pharmacology and Pharmacogenetics, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin, Turin, Italy.
Jessica CusatoLaboratory of Clinical Pharmacology and Pharmacogenetics, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin, Turin, Italy.
Miriam AntonucciLaboratory of Clinical Pharmacology and Pharmacogenetics, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin, Turin, Italy.
Alessandra MancaLaboratory of Clinical Pharmacology and Pharmacogenetics, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin, Turin, Italy.
Alice PalermitiLaboratory of Clinical Pharmacology and Pharmacogenetics, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin, Turin, Italy.
Catriona WaittDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Stephen WalimbwaInfectious Diseases Institute, Makerere University College of Health Sciences, P.O. Box 22418, Kampala, Uganda.
Mohammed LamordeInfectious Diseases Institute, Makerere University College of Health Sciences, P.O. Box 22418, Kampala, Uganda.
Giovanni di PerriLaboratory of Clinical Pharmacology and Pharmacogenetics, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin, Turin, Italy.
Antonio D'AvolioLaboratory of Clinical Pharmacology and Pharmacogenetics, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin, Turin, Italy.
Ospedale Amedeo di Savoia · ITInfectious Diseases Institute · UGUniversity of Liverpool · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRemdesivir 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.

objectivesThe validation of a reliable UHPLC-MS/MS method for remdesivir and GS-441524 quantification in human plasma.

methodsRemdesivir 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.

resultsAnalyte 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.

conclusionsThis method represents a useful tool for studying remdesivir and GS-441524 clinical pharmacokinetics, particularly during the current COVID-19 outbreak.

Indexed as

Adenosine MonophosphateAdenosine TriphosphateAlanineBetacoronavirusChromatography, High Pressure LiquidCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentHemorrhagic Fever, EbolaHumansPandemicsPneumonia, ViralSARS-CoV-2Sensitivity and SpecificityTandem Mass SpectrometryAdenosine MonophosphateAdenosine TriphosphateAlanineGS-441524 triphosphateremdesivir

Identifiers

PMID32361744
PMCPMC7197584
OpenAlexW3021344470

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.