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

USP
Palmitic acid, United States Pharmacopeia (USP) Reference Standard
Supelco
Palmitic acid, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Supelco
Palmitic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Myristic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Palmitic acid, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Sodium chloride, BioPerformance Certified, ≥99% (titration), suitable for insect cell culture, suitable for plant cell culture
Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Arachidic acid, synthetic, ≥99.0% (GC)
Supelco
Chloroform, suitable for HPLC, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
Sodium chloride solution, 0.85%
Sigma-Aldrich
Sodium chloride-35Cl, 99 atom % 35Cl
Sigma-Aldrich
Sodium chloride, random crystals, optical grade, 99.9% trace metals basis
Sigma-Aldrich
Behenic acid, 99%
Supelco
Palmitic acid, analytical standard
Sigma-Aldrich
Sodium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Supelco
Behenic acid, analytical standard
Supelco
Nonadecanoic acid, analytical standard
Supelco
Chloroform, analytical standard
Supelco
Myristic acid, analytical standard
Supelco
Methanol, analytical standard
Sigma-Aldrich
Sodium chloride, tested according to Ph. Eur.
Supelco
Palmitoleic acid, analytical standard
Supelco
Sodium chloride, reference material for titrimetry, certified by BAM, >99.5%
Sigma-Aldrich
Sodium chloride, 99.999% trace metals basis
Sigma-Aldrich
Myristic acid, natural, ≥98.5%, FG
Sigma-Aldrich
Sodium chloride, ≥99%, AR grade
Sigma-Aldrich
Lauric acid, natural, ≥98%, FCC, FG
Sigma-Aldrich
Chloroform, anhydrous, contains amylenes as stabilizer, ≥99%
Sigma-Aldrich
Chloroform, anhydrous, ≥99%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
Hexacosanoic acid, technical, ≥90% (GC)