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Using metabolomic techniques, we discovered common biomarkers for the prediction of hepatotoxicity in rat urine using mass spectrometry. For this purpose, liver toxicity was induced by 5\u2009days of oral administration of carbon tetrachloride (1\u2009ml\u2009kg<jats:sup>\u22121<\/jats:sup> per day), acetaminophen (1000\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> per day) and methotrexate (50\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> per day). Serum levels of alkaline phosphatase aspartate aminotransferase, alanine aminotransferase and histopathology in liver tissue were then checked to demonstrate liver toxicity. Global metabolic profiling with UPLC\u2010TOF\u2010MS (ultraperformance liquid chromatography\u2013mass spectrometry), multivariate analysis (partial least square\u2010discriminant analysis, hierarchical analysis) and database searching were performed to discover common biomarkers for liver toxicity induced by these three compounds. Urinary concentrations of the newly discovered biomarkers were then quantified to confirm them as biomarkers of hepatotoxicity with targeted metabolic profiling using GC (gas chromatography)\u2013MS and CE (capillary electrophoresis)\u2013MS. In the results, steroids, amino acids and bile acids were metabolically changed between the control and drug\u2010treated groups in global metabolic profiling; 11<jats:italic>\u03b2<\/jats:italic>\u2010hydroxyandrosterone, epiandrosterone, estrone, 11\u2010dehydrocorticosterone, glycine, alanine, valine, leucine, <jats:sc>dl<\/jats:sc>\u2010ornithine, 3\u2010methylhistidine, cholic acid and lithocholic acid were selected as liver toxicity biomarkers after performing targeted metabolic profiling. In conclusion, we discovered metabolite biomarkers belonging to three different metabolic pathways to check for liver toxicity with mass spectrometry from a metabolomics study that could be used to evaluate hepatotoxicity induced by drugs or other toxic compounds. Copyright \u00a9 2011 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1746","type":"journal-article","created":{"date-parts":[[2011,12,2]],"date-time":"2011-12-02T10:29:30Z","timestamp":1322821770000},"page":"505-520","source":"Crossref","is-referenced-by-count":52,"title":["Discovery of common urinary biomarkers for hepatotoxicity induced by carbon tetrachloride, acetaminophen and methotrexate by mass spectrometry\u2010based metabolomics"],"prefix":"10.1002","volume":"32","author":[{"given":"Bhowmik Salil","family":"Kumar","sequence":"first","affiliation":[{"name":"Biomolecular Functional Research Center Korea Institute of Science and Technology  PO Box\u2009131 Cheongryang Seoul 130\u2010650 Republic of Korea"},{"name":"University of Science and Technology  113 Gwahangno Yuseong\u2010gu Daejeon 305\u2010333 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bong Chul","family":"Chung","sequence":"additional","affiliation":[{"name":"Biomolecular Functional Research Center Korea Institute of Science and Technology  PO Box\u2009131 Cheongryang Seoul 130\u2010650 Republic of Korea"},{"name":"University of Science and Technology  113 Gwahangno Yuseong\u2010gu Daejeon 305\u2010333 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oh\u2010Seung","family":"Kwon","sequence":"additional","affiliation":[{"name":"Doping Control Center Korea Institute of Science and Technology  PO Box\u2009131 Cheongryang Seoul 130\u2010650 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Hwa","family":"Jung","sequence":"additional","affiliation":[{"name":"Biomolecular Functional Research Center Korea Institute of Science and Technology  PO Box\u2009131 Cheongryang Seoul 130\u2010650 Republic of Korea"},{"name":"University of Science and Technology  113 Gwahangno Yuseong\u2010gu Daejeon 305\u2010333 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440\u20101681.1999.03052.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447\u2010073X.2006.00129.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfn268"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.6.4.341"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1093\/clinchem\/30.10.1631","article-title":"Urinary excretion of acetaminophen and its metabolites as studied by proton NMR spectroscopy","volume":"30","author":"Bales JR","year":"1984","journal-title":"Clin. 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