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[Preprint]. 2021 Feb 5:2021.02.03.429628.
doi: 10.1101/2021.02.03.429628.

Development of a highly sensitive bioanalytical assay for the quantification of favipiravir

Paul Curley  1   2 , Megan Neary  1   2 , Usman Arshad  1   2 , Lee Tatham  1   2 , Henry Pertinez  1   2 , Helen Box  1   2 , Rajith Kr Rajoli  1   2 , Anthony Valentijn  1   2 , Joanne Sharp  1   2 , Steve P Rannard  3   2 , Andrew Owen  1   2
Affiliations

Development of a highly sensitive bioanalytical assay for the quantification of favipiravir

Paul Curley et al. bioRxiv. .

Abstract

Favipiravir (FAV; T-705) has been approved for use as an anti-influenza therapeutic and has reports against a wide range of viruses (e.g., Ebola virus, rabies and norovirus). Most recently FAV has been reported to demonstrate activity against SARS-CoV-2. Repurposing opportunities have been intensively studied with only limited success to date. If successful, repurposing will allow interventions to become more rapidly available than development of new chemical entities. Pre-clinical and clinical investigations of FAV require robust, reproducible and sensitive bioanalytical assay. Here, a liquid chromatography tandem mass spectrometry assay is presented which was linear from 0.78-200 ng/mL Accuracy and precision ranged between 89% and 110%, 101% and 106%, respectively. The presented assay here has applications in both pre-clinical and clinical research and may be used to facilitate further investigations into the application of FAV against SARS-CoV-2.

Keywords: COVID-19; Favipiravir; LC-MS/MS; SARS-CoV-2; plasma.

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Conflict of interest statement

Conflicts of interest statement AO and SR have received research funding from AstraZeneca and ViiV and consultancies from Gilead; AO has additionally received funding from Merck and Janssen and consultancies from ViiV and Merck not related to the current paper. No other conflicts are declared by the authors.

Figures

Figure 1
Figure 1
Figure 1 shows the percentage recovery for the low (a), medium (b) and high (c) QCs in extracted mouse plasma, human plasma and PBS. Data is show percentage of unextracted standards.
Figure 2
Figure 2
Figure 2 shows the standard curve generated from extracted mouse plasma, human plasma and PBS standards of FAV over the range of 0.78ng/mL to 200ng/ml.
Figure 3
Figure 3
Figure 3 shows a representative chromatogram from blank mouse plasma (A), blank human plasma (B) and blank PBS (C). Also shown is a representative chromatogram of the LLOQ in mouse plasma (D), human plasma (E) and PBS (F). The retention time of FAV is also shown (1.1 min).
See this image and copyright information in PMC

References

    1. Shiraki K. and Daikoku T., Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacology & therapeutics, 2020: p. 107512. - PMC - PubMed
    1. Delang L., Abdelnabi R., and Neyts J., Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral research, 2018. 153: p. 85–94. - PubMed
    1. Wang G., et al., Synthesis and anti-influenza activity of pyridine, pyridazine, and pyrimidine C-nucleosides as favipiravir (T-705) analogues. Journal of medicinal chemistry, 2016. 59(10): p. 4611–4624. - PubMed
    1. Kiso M., et al., T-705 (favipiravir) activity against lethal H5N1 influenza A viruses. Proceedings of the National Academy of Sciences, 2010. 107(2): p. 882–887. - PMC - PubMed
    1. Oestereich L., et al., Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral research, 2014. 105: p. 17–21. - PubMed

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