Evidence map›Paper›PMID 33548872›Full record

ArticleJournal of pharmaceutical and biomedical analysis2021

Simultaneous quantification of seven repurposed COVID-19 drugs remdesivir (plus metabolite GS-441524), chloroquine, hydroxychloroquine, lopinavir, ritonavir, favipiravir and azithromycin by a two-dimensional isotope dilution LC-MS/MS method in human serum.

Katharina Habler, Mathias Brügel, Daniel Teupser, Uwe Liebchen, Christina Scharf, Ulf Schönermarck, Michael Vogeser, Michael Paal

Open access · greenAbstract read
In one paragraph

Article in Journal of pharmaceutical and biomedical analysis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
12.1field-weighted citation impact, top 1% 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

38 citing papers in PubMed, 91 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Katharina HablerInstitute of Laboratory Medicine, University Hospital, LMU Munich, Germany.
Mathias BrügelInstitute of Laboratory Medicine, University Hospital, LMU Munich, Germany.
Daniel TeupserInstitute of Laboratory Medicine, University Hospital, LMU Munich, Germany.
Uwe LiebchenDepartment of Anesthesiology, University Hospital, LMU Munich, Germany.
Christina ScharfDepartment of Anesthesiology, University Hospital, LMU Munich, Germany.
Ulf SchönermarckDepartment of Medicine IV, University Hospital, LMU Munich, Germany.
Michael VogeserInstitute of Laboratory Medicine, University Hospital, LMU Munich, Germany.
Michael PaalInstitute of Laboratory Medicine, University Hospital, LMU Munich, Germany. Electronic address: Michael.Paal@med.uni-muenchen.de.
LMU Klinikum · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe present COVID-19 pandemic has prompted worldwide repurposing of drugs. The aim of the present work was to develop and validate a two-dimensional isotope-dilution liquid chromatrography tandem mass spectrometry (ID-LC-MS/MS) method for accurate quantification of remdesivir and its active metabolite GS-441524, chloroquine, hydroxychloroquine, lopinavir, ritonavir, favipiravir and azithromycin in serum; drugs that have gained attention for repurposing in the treatment of COVID-19.

methodsFollowing protein precipitation, samples were separated with a two-dimensional ultra-high performance liquid chromatography (2D-UHPLC) setup, consisting of an online solid phase extraction (SPE) coupled to an analytical column. For quantification, stable isotope-labelled analogues were used as internal standards for all analytes. The method was validated on the basis of the European Medicines Agency bioanalytical method validation protocol.

resultsDetuning of lopinavir and ritonavir allowed simultaneous quantification of all analytes with different concentration ranges and sensitivity with a uniform injection volume of 5 μL. The method provided robust validation results with inaccuracy and imprecision values of ≤ 9.59 % and ≤ 11.1 % for all quality controls.

conclusionThe presented method is suitable for accurate and simultaneous quantification of remdesivir, its metabolite GS-441525, chloroquine, hydroxychloroquine, lopinavir, ritonavir, favipiravir and azithromycin in human serum. The quantitative assay may be an efficient tool for the therapeutic drug monitoring of these potential drug candidates in COVID-19 patients in order to increase treatment efficacy and safety.

Indexed as

COVID-19 Drug TreatmentAdenosineAdenosine MonophosphateAlanineAmidesAntiviral AgentsAzithromycinChloroquineChromatography, LiquidCOVID-19FuransHumansHydroxychloroquineIsotopesLopinavirPandemicsAdenosineAdenosine MonophosphateAlanineAmidesAntiviral AgentsAzithromycinChloroquinefavipiravirFuransGS-441524HydroxychloroquineIsotopesLopinavirPyrazinesPyrrolesremdesivirRitonavirTriazinesAntiviral therapyIsotope dilution liquid chromatography tandem mass spectrometry (ID-LC–MS/MS)Therapeutic drug monitoring

Identifiers

PMID33548872
PMCPMC7843035
OpenAlexW3127514794

What OpenQuestion holds

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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.