Optimisation and validation of a sensitive bioanalytical method for niclosamide



Arshad, Usman, Pertinez, Henry, Box, Helen, Tatham, Lee ORCID: 0000-0001-9448-8876, Rajoli, Rajith KR ORCID: 0000-0002-6015-5712, Neary, Megan ORCID: 0000-0002-4960-2139, Sharp, Joanne, Valentijn, Anthony, Hobson, James ORCID: 0000-0003-2551-1774, Unsworth, Catherine
et al (show 6 more authors) (2021) Optimisation and validation of a sensitive bioanalytical method for niclosamide.

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Abstract

The SARS-CoV-2 pandemic has spread at an unprecedented rate, and 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. Niclosamide has been proposed as a candidate for repurposing for SARS-CoV-2 based upon the observation that it is amongst the most potent antiviral molecules evaluated in vitro . To investigate the pharmacokinetics of niclosamide, reliable, reproducible and sensitive bioanalytical assays are required. Here, a liquid chromatography tandem mass spectrometry assay is presented which was linear from 31.25-2000 ng/mL (high dynamic range) and 0.78-100 ng/mL (low dynamic range). Accuracy and precision ranged between 97.2% and 112.5%, 100.4% and 110.0%, respectively. The presented assay should have utility in preclinical evaluation of the exposure-response relationship and may be adapted for later evaluation of niclosamide in clinical trials.

Item Type: Article
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Faculty of Science and Engineering > School of Physical Sciences
Depositing User: Symplectic Admin
Date Deposited: 12 Aug 2021 09:09
Last Modified: 02 Aug 2022 07:12
DOI: 10.1101/2021.01.13.426426
Open Access URL: https://www.biorxiv.org/content/10.1101/2021.01.13...
URI: https://livrepository.liverpool.ac.uk/id/eprint/3133247