Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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Studies of Acetaminophen and Metabolites in Urine and Their Correlations with Toxicity Using Metabolomics

Author(s): Jinchun Sun, Laura K. Schnackenberg, Richard D. Beger.

Abstract:

A LC/MS-based metabolomic assay was utilized to investigate a drugs excretion kinetic profile in urine so that the drug toxicity information could be obtained. Groups of 10 male Sprague-Dawley rats per dose were orally gavaged with a single dose of 0.2% carboxymethylcellulose, 400 mg acetaminophen (APAP)/kg body weight or 1600 mg APAP/kg. UPLC/MS and NMR were used to evaluate the excretion kinetics of major drug metabolites. N-acetyl-Lcysteine acetaminophen (APAP-NAC) had statistically significant correlations with clinical chemistry data, endogenous metabolite concentrations and histopathology data. The potential toxicity of a drug can be assessed through the study of the drugs metabolite profiles.

Keywords: Acetaminophen, metabolite profile, liquid chromatography/mass spectrometry (LC/MS), NMR, principal component analysis, toxicity

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2009
Page: [130 - 136]
Pages: 7
DOI: 10.2174/187231209789352139
Price: $58