Abstract
A LC/MS-based metabolomic assay was utilized to investigate a drug's 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-L-cysteine 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 drug's metabolite profiles.
MeSH terms
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Acetaminophen / administration & dosage
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Acetaminophen / analogs & derivatives
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Acetaminophen / pharmacokinetics
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Acetaminophen / toxicity*
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Acetaminophen / urine*
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Administration, Oral
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Analgesics, Non-Narcotic / administration & dosage
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Analgesics, Non-Narcotic / pharmacokinetics
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Analgesics, Non-Narcotic / toxicity*
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Analgesics, Non-Narcotic / urine*
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Animals
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Biotransformation
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Chemical and Drug Induced Liver Injury / etiology*
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Chemical and Drug Induced Liver Injury / metabolism
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Chemical and Drug Induced Liver Injury / pathology
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Chromatography, Liquid
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Creatine / urine
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Dose-Response Relationship, Drug
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Liver / drug effects*
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Liver / metabolism
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Liver / pathology
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Magnetic Resonance Spectroscopy
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Male
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Mass Spectrometry
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Metabolomics* / methods
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Principal Component Analysis
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Rats
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Rats, Sprague-Dawley
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S-Adenosylmethionine / urine
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Sulfates / urine
Substances
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Analgesics, Non-Narcotic
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Sulfates
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Acetaminophen
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S-Adenosylmethionine
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acetaminophen glucuronide
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Creatine