LC/MS determination of the intracellular concentration of two novel aryl phosphoramidate prodrugs of PMPA and their metabolites in dog PBMC.
LC/MS assays were developed to determine the plasma and intracellular concentrations of two aryl phosphoramidate prodrugs of the nucleotide analog 9-[2-R-(phosphonomethoxy)propyl]adenine. LC/MS was used to demonstrate the presence of high concentrations of PMPA in peripheral blood mononucleocytes following oral administration of prodrugs in dogs. High concentrations of PMPA and active metabolite were detected in MT-2 cells incubated with prodrug using an ion-pairing LC/MS assay.
Lynch
T
T
Gilead Sciences, 333 Lakeside Drive, Foster City, California 94404, USA.
Eisenberg
G
G
Kernan
M
M
D000225:Adenine / Q000031:analogs & derivatives* / Q000097:blood*; D000577:Amides / Q000097:blood*; D000818:Animals; D002460:Cell Line; D002853:Chromatography, Liquid; D004285:Dogs; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D013058:Mass Spectrometry; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000097:blood*; D010756:Phosphoric Acids / Q000097:blood*; D011355:Prodrugs / Q000032:analysis*; D000068698:Tenofovir
D000577:Amides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D010756:Phosphoric Acids; D011355:Prodrugs; D000068698:Tenofovir; C011067:phosphoramidic acid; D000225:Adenine