title: Improved gas chromatographic-mass spectrometric determination of the N-methylcarbamoyl adduct at the N-terminal valine of globin, a metabolic product of the solvent N,N-dimethylformamide.
abstract: A sensitive method for determination of the N-methylcarbamoyl adduct at the N-terminal valine of globin, a new metabolic product of the industrial solvent N,N-dimethylformamide (DMF), has been developed and validated. The method includes conversion of the adduct by the Edman degradation to 3-methyl-5-isopropylhydantoin (MVH), which is followed by optimized gas chromatographic analysis with mass spectrometric detection at m/z 114. The recovery of MVH from terminal N-methylcarbamoylvaline was determined using a model dipeptide to be 90%. Calibration of the method is done with MVH, employing 3-methyl-5-isobutylhydantoin as the internal standard. The limit of detection is 0.2 nmol MVH/g globin when a 100-mg sample is used. Within- and between-day precision is 4-10%. The method has been used to determine the background levels of MVH in unexposed subjects. Further, toxicokinetic studies in volunteers laid the grounds for setting the reference value for biological monitoring of occupational exposure to DMF.
authors.affiliation: Centre of Industrial Hygiene and Occupational Diseases, National Institute of Public Health, Srobárova 48, 100 42 Prague, Czech Republic. jmraz@szu.cz
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Mráz
authors.forename: Sárka
authors.initials: S
authors.lastname: Dusková
authors.forename: Eva
authors.initials: E
authors.lastname: Gálová
authors.forename: Hana
authors.initials: H
authors.lastname: Nohová
authors.forename: Pavla
authors.initials: P
authors.lastname: Krausová
authors.forename: Igor
authors.initials: I
authors.lastname: Linhart
authors.forename: Petr
authors.initials: P
authors.lastname: Simek
mesh_terms: D002138:Calibration; D004126:Dimethylformamide / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D005914:Globins / Q000737:chemistry*; D006461:Hemolysis; D006801:Humans; D015203:Reproducibility of Results; D012997:Solvents; D014633:Valine / Q000737:chemistry*
chemical_list: D012997:Solvents; D004126:Dimethylformamide; D005914:Globins; D014633:Valine