Cargando…

Characterization of in-vivo human metabolites of the oral nucleoside anti-COVID-19 drug VV116 using UHPLC-Orbitrap-MS

VV116 is an oral nucleoside anti-COVID-19 drug undergoing clinical trials in China. We aimed to characterize its metabolites in plasma, urine, and feces of healthy Chinese male subjects after a single oral administration of 400 mg VV116, by using UHPLC-UV-Orbitrap-MS. After oral administration, VV11...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Ainan, Wang, Zhen, Diao, Xingxing, Zhong, Dafang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10008097/
https://www.ncbi.nlm.nih.gov/pubmed/36924632
http://dx.doi.org/10.1016/j.jpba.2023.115340
Descripción
Sumario:VV116 is an oral nucleoside anti-COVID-19 drug undergoing clinical trials in China. We aimed to characterize its metabolites in plasma, urine, and feces of healthy Chinese male subjects after a single oral administration of 400 mg VV116, by using UHPLC-UV-Orbitrap-MS. After oral administration, VV116 was almost completely converted into the metabolite 116-N1. Seventeen other metabolites produced by the subsequent metabolism of 116-N1 were also detected, including 6 phase I metabolites and 11 phase II metabolites resulting from hydrolysis, oxidative deamination, oxidation, and CN-group removal and conjugations. The results were exploratory. The major metabolite of VV116 in human plasma and urine was 116-N1, the main metabolites in feces were M2 and 116-N1. We then synthesized a reference M2 standard and confirmed its structure by MS and NMR.