title: 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.
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.
authors: University Medical Center of the Johannes Gutenberg University Mainz, Institute of Occupational, Social, and Environmental Medicine, Germany. rossbach@uni-mainz.de
authors: Bernd
authors: B
authors: Rossbach
authors: Peter
authors: P
authors: Kegel
authors: Stephan
authors: S
authors: Letzel
mesh_terms: D000328:Adult; D015415:Biomarkers; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006536:Heptanes / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D015394:Molecular Structure; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006536:Heptanes; C028618:n-heptane