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

• Published in: Clinical pharmacology and therapeutics Vol. 88; no. 6; p. 796
• Main 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
• Format: Journal Article
• Language: English
• Published: United States 01.12.2010
• Subjects: Adult; Chromatography, Liquid - methods; Drug Delivery Systems - methods; Humans; Intracellular Fluid - chemistry; Intracellular Fluid - metabolism; Leukocytes, Mononuclear - chemistry; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Male; Middle Aged; Tandem Mass Spectrometry - methods; Zidovudine - analysis; Zidovudine - blood; Zidovudine - metabolism
• ISSN: 1532-6535
• DOI: 10.1038/clpt.2010.188

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.