title: Development and application of a comparative fatty acid analysis method to investigate voriconazole-induced hepatotoxicity.
abstract: BACKGROUND
  As fatty acids play an important role in biological regulation, the profiling of fatty acid expression has been used to discover various disease markers and to understand disease mechanisms. This study developed an effective and accurate comparative fatty acid analysis method using differential labeling to speed up the metabolic profiling of fatty acids.
  
  
  METHODS
  Fatty acids were derivatized with unlabeled (D0) or deuterated (D3) methanol, followed by GC-MS analysis. The comparative fatty acid analysis method was validated using a series of samples with different ratios of D0/D3-labeled fatty acid standards and with mouse liver extracts.
  
  
  RESULTS
  Using a lipopolysaccharide (LPS)-treated mouse model, we found that the fatty acid profiles after LPS treatment were similar between the conventional single-sample analysis approach and the proposed comparative approach, with a Pearson's correlation coefficient of approximately 0.96. We applied the comparative method to investigate voriconazole-induced hepatotoxicity and revealed the toxicity mechanism as well as the potential of using fatty acids as toxicity markers.
  
  
  CONCLUSIONS
  In conclusion, the comparative fatty acid profiling technique was determined to be fast and accurate and allowed the discovery of potential fatty acid biomarkers in a more economical and efficient manner.
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Guan-yuan
authors.initials: GY
authors.lastname: Chen
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Huai-hsuan
authors.initials: HH
authors.lastname: Chiu
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shu-wen
authors.initials: SW
authors.lastname: Lin
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan; Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors.forename: Yufeng Jane
authors.initials: YJ
authors.lastname: Tseng
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Sung-jeng
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: kuoch@ntu.edu.tw.
authors.forename: Ching-hua
authors.initials: CH
authors.lastname: Kuo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D065819:Voriconazole / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D015415:Biomarkers; D005227:Fatty Acids; D065819:Voriconazole
keywords: Bioanalysis; Comparative fatty acid analysis; Gas chromatography-mass spectrometry; Hepatotoxicity; Stable isotope labeling; Voriconazole