title: Accelerator mass spectrometry measurement of intracellular concentrations of active drug metabolites in human target cells in vivo.
abstract: Accelerator mass spectrometry (AMS) is an ultrasensitive technique to detect radiolabeled compounds. We administered a microdose (100 µg) of (14)C-labeled zidovudine (ZDV) with or without a standard unlabeled dose (300 mg) to healthy volunteers. Intracellular ZDV-triphosphate (ZDV-TP) concentration was measured using AMS and liquid chromatography-tandem mass spectrometry (LC/MS/MS). AMS analysis yielded excellent concordance with LC/MS/MS and was 30,000-fold more sensitive. The kinetics of intracellular ZDV-TP formation changed several-fold over the dose range studied (100 µg-300 mg). AMS holds promise as a tool for quantifying intracellular drug metabolites and other biomediators in vivo.
authors.affiliation: Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: R C
authors.initials: RC
authors.lastname: Garner
authors.forename: L S
authors.initials: LS
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Seymour
authors.forename: E J
authors.initials: EJ
authors.lastname: Fuchs
authors.forename: W C
authors.initials: WC
authors.lastname: Hubbard
authors.forename: T L
authors.initials: TL
authors.lastname: Parsons
authors.forename: G E
authors.initials: GE
authors.lastname: Pakes
authors.forename: C V
authors.initials: CV
authors.lastname: Fletcher
authors.forename: C
authors.initials: C
authors.lastname: Flexner
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry / Q000379:methods*; D015215:Zidovudine / Q000032:analysis / Q000097:blood / Q000378:metabolism*
chemical_list: D015215:Zidovudine