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[Preprint]. 2021 Jan 15:2021.01.13.426426. [Version 1] doi: 10.1101/2021.01.13.426426

Optimisation and validation of a sensitive bioanalytical method for niclosamide

Usman Arshad, Henry Pertinez, Helen Box, Lee Tatham, Rajith KR Rajoli, Megan Neary, Joanne Sharp, Anthony Valentijn, James Hobson, Catherine Unsworth, Andrew Dwyer, Alison Savage, Tom O Mcdonald, Steve P Rannard, Paul Curley, Andrew Owen
PMCID: PMC7814822  PMID: 33469585

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.

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