Studies of acetaminophen and metabolites in urine and their correlations with toxicity using metabolomics.
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.
Sun
Jinchun
J
Division of Systems Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA.
Schnackenberg
Laura K
LK
Beger
Richard D
RD
D000082:Acetaminophen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine*; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine*; D000818:Animals; D001711:Biotransformation; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002853:Chromatography, Liquid; D003401:Creatine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000652:urine; D013431:Sulfates / Q000652:urine
D018712:Analgesics, Non-Narcotic; D013431:Sulfates; D000082:Acetaminophen; D012436:S-Adenosylmethionine; C037386:acetaminophen glucuronide; D003401:Creatine