Identification of a novel human circulating metabolite of tenofovir disoproxil fumarate with LC–MS/MS. (April 2015)

• Record Type: Journal Article
• Authors: Nye, Leanne C; Gray, Nicola; McClure, Myra; Boffit, Marta; Holmes, Elaine; Plumb, Robert S; Wilson, Ian D
• Is Part Of: Bioanalysis. Volume 7:Number 6(2015)
• Page Start: 643
• Page End: 652
• Publication Date: 2015-04
• Subjects: Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.14.300
• Languages: English
• ISSNs: 1757-6180

Abstract

Background: 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.