Quantitation of tizoxanide in multiple matrices to support cell culture, animal and human research



Neary, Megan ORCID: 0000-0002-4960-2139, Arshad, Usman, Tatham, Lee ORCID: 0000-0001-9448-8876, Pertinez, Henry, Box, Helen, Rajoli, Rajith KR ORCID: 0000-0002-6015-5712, Valentijn, Anthony, Sharp, Joanne, Rannard, Steve ORCID: 0000-0002-6946-1097, Biagini, Giancarlo ORCID: 0000-0001-6356-6595
et al (show 2 more authors) (2021) Quantitation of tizoxanide in multiple matrices to support cell culture, animal and human research. [Preprint]

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Abstract

Currently nitazoxanide is being assessed as a candidate therapeutic for SARS-CoV-2. Unlike many other candidates being investigated, tizoxanide (the active metabolite of nitazoxanide) plasma concentrations achieve antiviral levels after administration of the approved dose, although higher doses are expected to be needed to maintain these concentrations across the dosing interval in the majority of patients. Here an LC-MS/MS assay is described that has been validated in accordance with Food and Drug Administration (FDA) guidelines. Fundamental parameters have been evaluated, and these included accuracy, precision and sensitivity. The assay was validated for human plasma, mouse plasma and Dulbeccos Modified Eagles Medium (DMEM) containing varying concentrations of Foetal Bovine Serum (FBS). Matrix effects are a well-documented source of concern for chromatographic analysis, with the potential to impact various stages of the analytical process, including suppression or enhancement of ionisation. Therefore, a robustly validated LC-MS/MS analytical method is presented capable of quantifying tizoxanide in multiple matrices with minimal impact of matrix effects. The validated assay presented here was linear from 15.6ng/mL to 1000ng/mL. Accuracy and precision ranged between 102.2% and 113.5%, 100.1% and 105.4%, 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 nitazoxanide against SARS-CoV-2.

Item Type: Preprint
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: 21 Jul 2021 11:26
Last Modified: 04 Aug 2022 23:10
DOI: 10.1101/2021.05.27.445500
Open Access URL: https://pubmed.ncbi.nlm.nih.gov/34075381/
URI: https://livrepository.liverpool.ac.uk/id/eprint/3130834