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Accelerator Mass Spectrometry Measurement of Intracellular Concentrations of Active Drug Metabolites in Human Target Cells In Vivo
Author(s) -
Chen J,
Garner R C,
Lee L S,
Seymour M,
Fuchs E J,
Hubbard W C,
Parsons T L,
Pakes G E,
Fletcher C V,
Flexner C
Publication year - 2010
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2010.188
Subject(s) - microdose , in vivo , chemistry , intracellular , pharmacokinetics , mass spectrometry , zidovudine , pharmacology , metabolite , chromatography , liquid chromatography–mass spectrometry , tandem mass spectrometry , biochemistry , medicine , human immunodeficiency virus (hiv) , biology , virology , microbiology and biotechnology , viral disease
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 . Clinical Pharmacology & Therapeutics (2010) 88 6, 796–800. doi: 10.1038/clpt.2010.188
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