Accelerator mass spectrometry measurement of intracellular concentrations of active drug metabolites in human target cells in vivo

J. Chen, R. C. Garner, L. S. Lee, M. Seymour, E. J. Fuchs, W. C. Hubbard, T. L. Parsons, G. E. Pakes, C. V. Fletcher, C. Flexner

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Accelerator mass spectrometry (AMS) is an ultrasensitive technique to detect radiolabeled compounds. We administered a microdose (100 νg) of 14 C-labeled zidovudine (ZDV) with or without a standard unlabeled dose (300mg) 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 (100νg-300mg). AMS holds promise as a tool for quantifying intracellular drug metabolites and other biomediators in vivo.

Original languageEnglish (US)
Pages (from-to)796-800
Number of pages5
JournalClinical Pharmacology and Therapeutics
Volume88
Issue number6
DOIs
StatePublished - Dec 2010

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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