Studies of Acetaminophen and Metabolites in Urine and Their Correlations with Toxicity Using Metabolomics
Laura K. Schnackenberg,
Richard D. Beger.
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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