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10.1016/j.ab.2021.114118

http://scihub22266oqcxt.onion/10.1016/j.ab.2021.114118
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suck abstract from ncbi


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pmid33508271      Anal+Biochem 2021 ; 617 (ä): 114118
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  • Validation of LC-MS/MS methods for determination of remdesivir and its metabolites GS-441524 and GS-704277 in acidified human plasma and their application in COVID-19 related clinical studies #MMPMID33508271
  • Xiao D; John Ling KH; Tarnowski T; Humeniuk R; German P; Mathias A; Chu J; Chen YS; van Ingen E
  • Anal Biochem 2021[Mar]; 617 (ä): 114118 PMID33508271show ga
  • Remdesivir (RDV) is a phosphoramidate prodrug designed to have activity against a broad spectrum of viruses. Following IV administration, RDV is rapidly distributed into cells and tissues and simultaneously metabolized into GS-441524 and GS-704277 in plasma. LC-MS/MS methods were validated for determination of the 3 analytes in human plasma that involved two key aspects to guarantee their precision, accuracy and robustness. First, instability issues of the analytes were overcome by diluted formic acid (FA) treatment of the plasma samples. Secondly, a separate injection for each analyte was performed with different ESI modes and organic gradients to achieve sensitivity and minimize carryover. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column (2.1 x 50 mm, 1.8 mum) with a run time of 3.4 min. The calibration ranges were 4-4000, 2-2000, and 2-2000 ng/mL, respectively for RDV, GS-441524 and GS-704277. The intraday and interday precision (%CV) across validation runs at 3 QC levels for all 3 analytes was less than 6.6%, and the accuracy was within +/-11.5%. The long-term storage stability in FA-treated plasma was established to be 392, 392 and 257 days at -70 degrees C, respectively for RDV, GS-441524 and GS-704277. The validated method was successfully applied in COVID-19 related clinical studies.
  • |Adenosine Monophosphate/*analogs & derivatives/blood[MESH]
  • |Adenosine/analogs & derivatives[MESH]
  • |Alanine/*analogs & derivatives/blood[MESH]
  • |Antiviral Agents/*blood[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |Chromatography, High Pressure Liquid/methods[MESH]
  • |Drug Monitoring/*methods[MESH]
  • |Furans/*blood[MESH]
  • |Humans[MESH]
  • |Limit of Detection[MESH]
  • |Pyrroles/*blood[MESH]
  • |Tandem Mass Spectrometry/*methods[MESH]


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