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

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...