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Detection of Remdesivir by Liquid Chromatography with Tandem Mass Spectrometry in a Patient with SARS-CoV-2 Infection

Publication at First Faculty of Medicine, Faculty of Physical Education and Sport, Central Library of Charles University, Second Faculty of Medicine |
2022

Abstract

One of the officially approved medications for the treatment of the pandemic disease COVID-19, caused by the SARS-CoV-2 virus, is remdesivir. This antiviral mole-cule is a prodrug that is metabolized into its active form (an ATP analogue).

Because of its hepatotoxicity and ne-phrotoxicity, it is necessary to monitor the serum concentrations of remdesivir. For the therapeutic drug monitoring of remdesivir, a method using liquid chromatography with tandem mass spectrometry (LC-MS/MS) in positive elec-trospray ionization mode was developed.

Mass detection was done via triple quadrupole in the Multiple reaction monitoring mode. Separation was done on Zorbax C18 column at 35 °C in mobile phase gradient and flow 0.4 mL min-1 (A - 0.1% formic acid in water, B - 0.1% formic acid in 95% acetonitrile).

Time of analysis was 4 minutes. LC-MS/MS method was successfully validated.

Calibration was done in blood serum and plasma and it was linear in the range of tested concentrations (0-1000 ng mL-1). Samples were prepared by protein precipitation.

The method was used to measure remdesivir concentration in a patient with SARS-CoV-2 infection. The measured concentration 60 minutes after remdesivir application was 175+-15 ng mL-1.