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

Neary, Megan, Arshad, Usman, Tatham, Lee, Pertinez, Henry, Box, Helen, Rajoli, Rajith K R, Valentijn, Anthony, Sharp, Joanne, Rannard, Steve P, Biagini, Giancarlo ORCID: https://orcid.org/0000-0001-6356-6595, Curley, Paul and Owen, Andrew (2023) 'Quantitation of tizoxanide in multiple matrices to support cell culture, animal and human research'. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, Vol 1228, e123823.

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Abstract

Currently nitazoxanide is being assessed as a candidate therapeutic for SARS-CoV-2. Nitazoxanide is rapidly broken down to its active metabolite tizoxanide upon administration. Unlike many other candidates being investigated, tizoxanide 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 Dulbecco's 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. Herein a 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 15.6 ng/mL to 1000 ng/mL. 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:	Article
Subjects:	WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 506 COVID-19
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.jchromb.2023.123823
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	14 Aug 2023 08:10
Last Modified:	14 Aug 2023 08:10
URI:	https://archive.lstmed.ac.uk/id/eprint/22957

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