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10.1515/cclm-2020-0612

http://scihub22266oqcxt.onion/10.1515/cclm-2020-0612
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32573468!ä!32573468

suck abstract from ncbi


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pmid32573468      Clin+Chem+Lab+Med 2020 ; 58 (9): 1461-1468
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  • Quantification of plasma remdesivir and its metabolite GS-441524 using liquid chromatography coupled to tandem mass spectrometry Application to a Covid-19 treated patient #MMPMID32573468
  • Alvarez JC; Moine P; Etting I; Annane D; Larabi IA
  • Clin Chem Lab Med 2020[Aug]; 58 (9): 1461-1468 PMID32573468show ga
  • OBJECTIVES: A method based on liquid chromatography coupled to triple quadrupole mass spectrometry detection using 50 microL of plasma was developed and fully validated for quantification of remdesivir and its active metabolites GS-441524. METHODS: A simple protein precipitation was carried out using 75 microL of methanol containing the internal standard (IS) remdesivir-13C6 and 5 microL ZnSO4 1 M. After separation on Kinetex(R) 2.6 microm Polar C18 100A LC column (100 x 2.1 mm i.d.), both compounds were detected by a mass spectrometer with electrospray ionization in positive mode. The ion transitions used were m/z 603.3 --> m/z 200.0 and m/z 229.0 for remdesivir, m/z 292.2 --> m/z 173.1 and m/z 147.1 for GS-441524 and m/z 609.3 --> m/z 206.0 for remdesivir-13C6. RESULTS: Calibration curves were linear in the 1-5000 mug/L range for remdesivir and 5-2500 for GS-441524, with limit of detection set at 0.5 and 2 mug/L and limit of quantification at 1 and 5 mug/L, respectively. Precisions evaluated at 2.5, 400 and 4000 mug/L for remdesivir and 12.5, 125, 2000 mug/L for GS-441524 were lower than 14.7% and accuracy was in the [89.6-110.2%] range. A slight matrix effect was observed, compensated by IS. Higher stability of remdesivir and metabolite was observed on NaF-plasma. After 200 mg IV single administration, remdesivir concentration decrease rapidly with a half-life less than 1 h while GS-441524 appeared rapidly and decreased slowly until H24 with a half-life around 12 h. CONCLUSIONS: This method would be useful for therapeutic drug monitoring of these compounds in Covid-19 pandemic.
  • |*Betacoronavirus[MESH]
  • |Adenosine Monophosphate/*analogs & derivatives/blood/pharmacokinetics[MESH]
  • |Adenosine/analogs & derivatives[MESH]
  • |Alanine/*analogs & derivatives/blood/pharmacokinetics[MESH]
  • |Antiviral Agents/*blood/pharmacokinetics[MESH]
  • |COVID-19[MESH]
  • |Chromatography, Liquid/*methods[MESH]
  • |Coronavirus Infections/*blood[MESH]
  • |Drug Monitoring/*methods[MESH]
  • |Drug Stability[MESH]
  • |Female[MESH]
  • |Furans/*blood/pharmacokinetics[MESH]
  • |Humans[MESH]
  • |Limit of Detection[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*blood[MESH]
  • |Pyrroles/*blood/pharmacokinetics[MESH]
  • |Reproducibility of Results[MESH]
  • |SARS-CoV-2[MESH]
  • |Tandem Mass Spectrometry/*methods[MESH]


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