Identification of a novel human circulating metabolite of tenofovir disoproxil fumarate with LC-MS/MS

Leanne C. Nye; Nicola Gray; Myra McClure; Marta Boffit; Elaine Holmes; Robert S. Plumb; Ian D. Wilson

doi:10.4155/bio.14.300

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Identification of a novel human circulating metabolite of tenofovir disoproxil fumarate with LC-MS/MS

Journal article

Peer reviewed

Identification of a novel human circulating metabolite of tenofovir disoproxil fumarate with LC-MS/MS

Leanne C. Nye, Nicola Gray, Myra McClure, Marta Boffit, Elaine Holmes, Robert S. Plumb and Ian D. Wilson

Bioanalysis, Vol.7(6), pp.643-652

2015

DOI: https://doi.org/10.4155/bio.14.300

PMID: 25871584

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Abstract

Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug used for the treatment of Human Immunodeficiency Virus and Hepatitis B infections. Results: A metabolite that has previously not been observed in the circulation of humans was detected by LC–MS/MS in early time point plasma samples following administration of TDF to healthy volunteers. The metabolite was identified using a range of LC–MS/MS-based techniques as a monoester of TDF, derived from the partially hydrolyzed bis-ester prodrug. TDF, when spiked into plasma, was observed to degrade first to the putative monoester and subsequently to tenofovir. Conclusion: The presence of this unstable metabolite in some samples has implications for sample collection, handling and storage in studies of tenofovir where serum concentrations are determined.

Details

Title: Identification of a novel human circulating metabolite of tenofovir disoproxil fumarate with LC-MS/MS
Authors/Creators: Leanne C. Nye - Imperial College London
Nicola Gray - Imperial College London
Myra McClure - Imperial College London
Marta Boffit - Imperial College London
Elaine Holmes - Imperial College London
Robert S. Plumb - Imperial College London
Ian D. Wilson - Imperial College London
Publication Details: Bioanalysis, Vol.7(6), pp.643-652
Publisher: Future Sci Ltd
Number of pages: 10
Grant note: Bruker Biospin Metabometrix MC_PC_12025 / UK Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Imperial College MC_PC_12025 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission Waters Corporation National Institute of Health Research (England); National Institute for Health Research (NIHR) MC_PC_12025 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 991005598619707891
Copyright: © 2015 Future Science Ltd
Murdoch Affiliation: Centre for Computational and Systems Medicine
Language: English
Resource Type: Journal article

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Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.1372 HIV Comorbidities
Web Of Science research areas: Biochemical Research Methods; Chemistry, Analytical
ESI research areas: Biology & Biochemistry