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- Title
Accelerator Mass Spectrometry Measurement of Intracellular Concentrations of Active Drug Metabolites in Human Target Cells In Vivo.
- Authors
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.
- Abstract
Accelerator mass spectrometry (AMS) is an ultrasensitive technique to detect radiolabeled compounds. We administered a microdose (100 µg) of 14C-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.
- Subjects
ACCELERATOR mass spectrometry; METABOLITES; DRUG metabolism; RADIOACTIVE tracers; LIQUID chromatography; AZIDOTHYMIDINE
- Publication
Clinical Pharmacology & Therapeutics, 2010, Vol 88, Issue 6, p796
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2010.188