Skip to Content
Merck
  • Development and application of a comparative fatty acid analysis method to investigate voriconazole-induced hepatotoxicity.

Development and application of a comparative fatty acid analysis method to investigate voriconazole-induced hepatotoxicity.

Clinica chimica acta; international journal of clinical chemistry (2014-08-26)
Guan-yuan Chen, Huai-hsuan Chiu, Shu-wen Lin, Yufeng Jane Tseng, Sung-jeng Tsai, Ching-hua Kuo
ABSTRACT

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. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Arachidonic acid, from non-animal source, ≥98.5% (GC)
Sigma-Aldrich
Stearic acid, ≥95%, FCC, FG
Supelco
Oleic acid, analytical standard
Sigma-Aldrich
Oleic acid, natural, FCC
Supelco
cis-11-Eicosenoic acid, analytical standard
Sigma-Aldrich
Arachidonic acid, >95.0% (GC)
Supelco
Elaidic acid, analytical standard
Sigma-Aldrich
Oleic acid, technical grade, 90%
Supelco
Nervonic acid, analytical standard
Sigma-Aldrich
Myristoleic acid, ≥99% (capillary GC)
Sigma-Aldrich
Nervonic acid, ≥99% (capillary GC)
Sigma-Aldrich
cis-8,11,14-Eicosatrienoic acid, ≥99%
Sigma-Aldrich
Oleic acid, ≥99% (GC)
Sigma-Aldrich
cis-11-Eicosenoic acid, ≥99% (capillary GC)
Sigma-Aldrich
Tricosanoic acid, ≥99% (capillary GC)
Sigma-Aldrich
Elaidic acid, ≥99.0% (GC)
Sigma-Aldrich
Oleic acid, BioReagent, suitable for cell culture
Sigma-Aldrich
Stearic acid, Grade I, ≥98.5% (capillary GC)
Stearic acid, European Pharmacopoeia (EP) Reference Standard
Supelco
Oleic acid, Selectophore, ≥99%
Supelco
Residual Solvent - Chloroform, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Stearic acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Acetyl chloride, reagent grade, 98%
Sigma-Aldrich
Acetyl chloride, reagent grade, 98%
Supelco
Dodecanoic acid, analytical standard
Sigma-Aldrich
Dodecanoic acid, ≥99% (GC/titration)
Sigma-Aldrich
Dodecanoic acid, 98%
Supelco
Stearic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Stearic acid, analytical standard
Supelco
Stearic acid, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland