Application of headspace solid phase dynamic extraction gas chromatography/mass spectrometry (HS-SPDE-GC/MS) for biomonitoring of n-heptane and its metabolites in blood

Toxicol Lett. 2012 Apr 25;210(2):232-9. doi: 10.1016/j.toxlet.2011.07.033. Epub 2011 Aug 31.

Abstract

Solid phase dynamic extraction (SPDE) is an innovative sample preparation and enrichment technique in connection with gas chromatography (GC). Using SPDE, we developed a method for simultaneous determination of n-heptane and its mono-oxygenated metabolites heptane-4-one, 3-one, 2-one, 4-ol, 3-ol, 2-ol, and 1-ol in blood. After adjustment of various extraction and desorption parameters, method validation resulted in limits of detection (LOD) between 0.006 (heptane-4-one) and 0.021mg/L (heptane-1-ol). Intra-assay coefficients of variation ranged between 4.8% and 20.8% while relative recovery ranged between 100% and 117% (spiked concentration 0.128mg/L, n=8). The method was applied to blood samples, which have been collected from 20 volunteers after controlled inhalative exposure to 167, 333, and 500ppm n-heptane. After 3h of exposure, n-heptane and heptane-2-one were detectable in all samples in concentrations ranging up to 2.903 and 0.495mg/L, while the concentrations of the remaining analytes were closer to the respective LOD or even below. A significant linear relationship with ambient exposure (R(2)=0.701, p<0.001, n=55) was found for n-heptane in blood, which could be helpful for evaluation of biological exposure limits in future. Due to its high abundance in blood, 2-heptanone could be an interesting candidate as a biomarker also in alternative matrices such as urine or saliva.

MeSH terms

  • Adult
  • Biomarkers
  • Dose-Response Relationship, Drug
  • Environmental Exposure
  • Environmental Monitoring / methods*
  • Gas Chromatography-Mass Spectrometry / methods*
  • Heptanes / administration & dosage
  • Heptanes / blood*
  • Heptanes / chemistry
  • Heptanes / metabolism*
  • Humans
  • Inhalation Exposure
  • Male
  • Molecular Structure
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Biomarkers
  • Heptanes
  • n-heptane