Toxicology letters

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.

PMID 21903155


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.