"One-pot" ethyl chloroformate derivatization and liquid-liquid extraction of reduced glutathione in erythrocyte and its quantitative GC-MS analysis

J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Dec 1:1070:15-22. doi: 10.1016/j.jchromb.2017.10.030. Epub 2017 Oct 20.

Abstract

A simple "one-pot" derivatization and liquid-liquid extraction (LLE) procedure was developed for GC-MS analysis of reduced glutathione (GSH) analysis in erythrocytes. The metabolite was extracted by 5% (w/v) TCA, the supernatant treated with ECF and ethanol-pyridine media, the derivative separated and detected by gas chromatography-mass spectrometry using a short non-polar capillary GC column at a high column-head pressure. Total analysis time was 11min. The process was optimized by a Design of Experiment. The method was validated showing a good linearity over the 25.4-813.4μM concentration range, providing satisfactory results in terms of intra-day and inter-day precision as well as an optimal accuracy. The new method was evaluated in a pilot study involving patients with severe protein malnutrition. Comparison of this group with a group of healthy subjects revealed significantly lower GSH concentrations in erythrocytes in the former, thus proving that the described GC-MS method could be employed for fast and simple GSH analysis in clinical studies.

Keywords: Chloroformate derivatization; Erythrocytes; Gas chromatography-mass spectrometry; Glutathione.

MeSH terms

  • Erythrocytes / chemistry*
  • Formic Acid Esters / chemistry*
  • Gas Chromatography-Mass Spectrometry / methods*
  • Glutathione / blood*
  • Glutathione / chemistry
  • Glutathione / isolation & purification*
  • Humans
  • Limit of Detection
  • Linear Models
  • Liquid-Liquid Extraction / methods*
  • Pilot Projects
  • Reproducibility of Results

Substances

  • Formic Acid Esters
  • ethyl chloroformate
  • Glutathione