title: Simultaneous quantification of haemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile, acrylamide and glycidamide in human blood by isotope-dilution GC/NCI-MS/MS.
abstract: Haemoglobin adducts are highly valuable biomarkers of cumulative exposure to carcinogenic substances. We have developed and applied an analytical method for the simultaneous quantification of five haemoglobin adducts of important occupational and environmental carcinogens. The N-terminal adducts were determined with gas chromatography as pentafluorophenylthiohydantoine derivatives according to the modified Edman-procedure and subsequent acetonization of the glycidamide adduct N-(R,S)-2-hydroxy-2-carbamoylethylvaline (GAVal). The use of self-synthesized labelled internal standards in combination with tandem mass spectrometry using negative chemical ionisation guarantees both high accuracy and sensitivity of our determination. The limit of detection for N-2-hydroxyethylvaline (HEVal), N-(R,S)-2-hydroxypropylvaline (HPVal), N-2-carbamoylethylvaline (AAVal) and N-(R,S)-2-hydroxy-2-carbamoylethylvaline (GAVal) was 2 pmol/g globin, for N-2-cyanoethylvaline (CEVal) it was determined as 0.5 pmol/g globin, which was sufficient to determine the background levels of these adducts in the non-smoking general population. The between-day-precision for all analytes using a human blood sample as quality control material ranged from 4.7 to 12.3%. We investigated blood samples of a small group (n=104) of non-smoking persons of the general population for the background levels of these haemoglobin adducts. The median values for HEVal, HPVal, CEVal, AAVal and GAVal in a group of 92 non-smoking persons were 18.1, 4.1, <0.5, 29.9 and 35.2 pmol/g globin, respectively. The adduct levels in 12 persons reporting exposure to passive smoke at home were similar for most adducts with median values of 17.2, 4.1, 1.0, 24.9 and 29.7 pmol/g globin for HEVal, HPVal, CEVal, AAVal and GAVal, respectively. Our results point to an elevated uptake of acrylonitrile caused by passive smoking as indicated by higher levels of the corresponding haemoglobin adduct CEVal.
authors.affiliation: Institute for Occupational and Social Medicine, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany. tschettgen@ukaachen.de
authors.forename: T
authors.initials: T
authors.lastname: Schettgen
authors.forename: J
authors.initials: J
authors.lastname: Müller
authors.forename: H
authors.initials: H
authors.lastname: Fromme
authors.forename: J
authors.initials: J
authors.lastname: Angerer
mesh_terms: D020106:Acrylamide / Q000097:blood* / Q000737:chemistry; D000181:Acrylonitrile / Q000097:blood* / Q000737:chemistry; D002138:Calibration; D004781:Environmental Exposure; D004852:Epoxy Compounds / Q000097:blood* / Q000737:chemistry; D005027:Ethylene Oxide / Q000097:blood* / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006454:Hemoglobins / Q000032:analysis* / Q000737:chemistry; D006801:Humans; D057230:Limit of Detection; D010865:Pilot Projects; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004852:Epoxy Compounds; D006454:Hemoglobins; D020106:Acrylamide; C071834:glycidamide; D005027:Ethylene Oxide; D000181:Acrylonitrile; C009068:propylene oxide