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Quantitative HPLC-MS/MS determination of Nuc, the active metabolite of remdesivir, and its pharmacokinetics in rat.
Du, Ping; Wang, Guoyong; Yang, Song; Li, Pengfei; Liu, Lihong.
  • Du P; Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti South Road, Chaoyang District, Beijing, 100020, People's Republic of China. pingdu2012@163.com.
  • Wang G; Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti South Road, Chaoyang District, Beijing, 100020, People's Republic of China.
  • Yang S; Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti South Road, Chaoyang District, Beijing, 100020, People's Republic of China.
  • Li P; Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti South Road, Chaoyang District, Beijing, 100020, People's Republic of China.
  • Liu L; Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti South Road, Chaoyang District, Beijing, 100020, People's Republic of China. liulihong@bjcyh.com.
Anal Bioanal Chem ; 413(23): 5811-5820, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1321733
ABSTRACT
Remdesivir is a nucleotide analog prodrug that has received much attention since the outbreak of the COVID-19 pandemic in December 2019. GS-441524 (Nuc) is the active metabolite of remdesivir and plays a pivotal role in the clinical treatment of COVID-19. Here, a robust HPLC-MS/MS method was developed to determine Nuc concentrations in rat plasma samples after a one-step protein precipitation process. Chromatographic separation was accomplished on Waters XBrige C18 column (50 × 2.1 mm, 3.5 µm) under gradient elution conditions. Multiple reaction monitoring transitions in electrospray positive ion mode were m/z 292.2 → 163.2 for Nuc and 237.1 → 194.1 for the internal standard (carbamazepine). The quantitative analysis method was fully validated in line with the United States Food and Drug Administration guidelines. The linearity, accuracy and precision, matrix effect, recovery, and stability results met the requirements of the guidelines. Uncertainty of measurement and incurred sample reanalysis were analyzed to further ensure the robustness and reproducibility of the method. This optimized method was successfully applied in a rat pharmacokinetics study of remdesivir (intravenously administration, 5 mg kg-1). The method can act as a basis for further pharmacokinetic and clinical efficacy investigations in patients with COVID-19. Graphical abstract.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Adenosine / Adenosine Monophosphate / Chromatography, High Pressure Liquid / Alanine / Tandem Mass Spectrometry Type of study: Clinical Practice Guide Limits: Animals Language: English Journal: Anal Bioanal Chem Year: 2021 Document Type: Article

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Adenosine / Adenosine Monophosphate / Chromatography, High Pressure Liquid / Alanine / Tandem Mass Spectrometry Type of study: Clinical Practice Guide Limits: Animals Language: English Journal: Anal Bioanal Chem Year: 2021 Document Type: Article