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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.
Habler, Katharina; Brügel, Mathias; Teupser, Daniel; Liebchen, Uwe; Scharf, Christina; Schönermarck, Ulf; Vogeser, Michael; Paal, Michael.
  • Habler K; Institute of Laboratory Medicine, University Hospital, LMU Munich, Germany.
  • Brügel M; Institute of Laboratory Medicine, University Hospital, LMU Munich, Germany.
  • Teupser D; Institute of Laboratory Medicine, University Hospital, LMU Munich, Germany.
  • Liebchen U; Department of Anesthesiology, University Hospital, LMU Munich, Germany.
  • Scharf C; Department of Anesthesiology, University Hospital, LMU Munich, Germany.
  • Schönermarck U; Department of Medicine IV, University Hospital, LMU Munich, Germany.
  • Vogeser M; Institute of Laboratory Medicine, University Hospital, LMU Munich, Germany.
  • Paal M; Institute of Laboratory Medicine, University Hospital, LMU Munich, Germany. Electronic address: Michael.Paal@med.uni-muenchen.de.
J Pharm Biomed Anal ; 196: 113935, 2021 Mar 20.
Article in English | MEDLINE | ID: covidwho-1051795
Semantic information from SemMedBD (by NLM)
1. Radioisotope Dilution Technique USES Liquid Chromatography Mass Spectrometry
Subject
Radioisotope Dilution Technique
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USES
Object
Liquid Chromatography Mass Spectrometry
2. Serum PART_OF Homo sapiens
Subject
Serum
Predicate
PART_OF
Object
Homo sapiens
3. Serum LOCATION_OF chloroquine
Subject
Serum
Predicate
LOCATION_OF
Object
chloroquine
4. Serum LOCATION_OF hydroxychloroquine
Subject
Serum
Predicate
LOCATION_OF
Object
hydroxychloroquine
5. Serum LOCATION_OF azithromycin
Subject
Serum
Predicate
LOCATION_OF
Object
azithromycin
6. Serum LOCATION_OF ritonavir
Subject
Serum
Predicate
LOCATION_OF
Object
ritonavir
7. Serum LOCATION_OF lopinavir
Subject
Serum
Predicate
LOCATION_OF
Object
lopinavir
8. Serum LOCATION_OF favipiravir
Subject
Serum
Predicate
LOCATION_OF
Object
favipiravir
9. Pharmaceutical Preparations TREATS COVID-19
Subject
Pharmaceutical Preparations
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TREATS
Object
COVID-19
10. Serum LOCATION_OF CD69 protei
Subject
Serum
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LOCATION_OF
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CD69 protei
11. High pressure liquid chromatography procedure USES ultra
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High pressure liquid chromatography procedure
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USES
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ultra
12. Therapeutic Drug Monitoring TREATS COVID-19
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Therapeutic Drug Monitoring
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TREATS
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COVID-19
13. COVID-19 PROCESS_OF Patients
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COVID-19
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PROCESS_OF
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Patients
14. Therapeutic Drug Monitoring TREATS Patients
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Therapeutic Drug Monitoring
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TREATS
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Patients
15. Radioisotope Dilution Technique USES Liquid Chromatography Mass Spectrometry
Subject
Radioisotope Dilution Technique
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USES
Object
Liquid Chromatography Mass Spectrometry
16. Serum PART_OF Homo sapiens
Subject
Serum
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PART_OF
Object
Homo sapiens
17. Serum LOCATION_OF chloroquine
Subject
Serum
Predicate
LOCATION_OF
Object
chloroquine
18. Serum LOCATION_OF hydroxychloroquine
Subject
Serum
Predicate
LOCATION_OF
Object
hydroxychloroquine
19. Serum LOCATION_OF azithromycin
Subject
Serum
Predicate
LOCATION_OF
Object
azithromycin
20. Serum LOCATION_OF ritonavir
Subject
Serum
Predicate
LOCATION_OF
Object
ritonavir
21. Serum LOCATION_OF lopinavir
Subject
Serum
Predicate
LOCATION_OF
Object
lopinavir
22. Serum LOCATION_OF favipiravir
Subject
Serum
Predicate
LOCATION_OF
Object
favipiravir
23. Pharmaceutical Preparations TREATS COVID-19
Subject
Pharmaceutical Preparations
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TREATS
Object
COVID-19
24. Serum LOCATION_OF CD69 protein, human|CD69
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Serum
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CD69 protein, human|CD69
25. High pressure liquid chromatography procedure USES ultra
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High pressure liquid chromatography procedure
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ultra
26. Therapeutic Drug Monitoring TREATS COVID-19
Subject
Therapeutic Drug Monitoring
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TREATS
Object
COVID-19
27. COVID-19 PROCESS_OF Patients
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COVID-19
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PROCESS_OF
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Patients
28. Therapeutic Drug Monitoring TREATS Patients
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Therapeutic Drug Monitoring
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ABSTRACT

BACKGROUND:

The 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.

METHODS:

Following 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.

RESULTS:

Detuning 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.

CONCLUSION:

The 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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Antiviral Agents / SARS-CoV-2 / COVID-19 / Isotopes Subject: Antiviral Agents / SARS-CoV-2 / COVID-19 / Isotopes Language: English Journal: J Pharm Biomed Anal Clinical aspect: Therapy Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Antiviral Agents / SARS-CoV-2 / COVID-19 / Isotopes Subject: Antiviral Agents / SARS-CoV-2 / COVID-19 / Isotopes Language: English Journal: J Pharm Biomed Anal Clinical aspect: Therapy Year: 2021
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