A procedure for the determination of haemoglobin adducts formed by exposure to methyl bromide was evaluated as a possible method for the measurement of a biological index of exposure to the alkylating agent. The reaction products after in vitro incubation were used to design the chemical syntheses of deuterated peptides corresponding to the tryptic peptides where the modified residues had been identified. These peptides were used as standards for the quantitative evaluation of real samples. The correlation coefficient was r = 0.998 in the range 2.5-20 ppm. The relative standard deviation was about 3%. Blood samples were digested with trypsin and the mixture was analysed by liquid chromatography/electrospray mass spectrometry through selected ion monitoring of the mass signal relative to the modified peptides. The analysis of blood samples from workers exposed to methyl bromide demonstrated the usefulness of this mass spectrometric-based method for the monitoring of human exposure to the genotoxic alkylating agent via the synthesis of suitable peptide standards. This procedure is the first alternative method to the well established monitoring of N-terminal adducts, the latter not being applicable to all alkylating agents.

Biomonitoring of human exposure to methyl bromide by isotope dilution mass spectrometry of peptide adducts

Mamone;Malorni;
1999

Abstract

A procedure for the determination of haemoglobin adducts formed by exposure to methyl bromide was evaluated as a possible method for the measurement of a biological index of exposure to the alkylating agent. The reaction products after in vitro incubation were used to design the chemical syntheses of deuterated peptides corresponding to the tryptic peptides where the modified residues had been identified. These peptides were used as standards for the quantitative evaluation of real samples. The correlation coefficient was r = 0.998 in the range 2.5-20 ppm. The relative standard deviation was about 3%. Blood samples were digested with trypsin and the mixture was analysed by liquid chromatography/electrospray mass spectrometry through selected ion monitoring of the mass signal relative to the modified peptides. The analysis of blood samples from workers exposed to methyl bromide demonstrated the usefulness of this mass spectrometric-based method for the monitoring of human exposure to the genotoxic alkylating agent via the synthesis of suitable peptide standards. This procedure is the first alternative method to the well established monitoring of N-terminal adducts, the latter not being applicable to all alkylating agents.
1999
alkylating agent
deuterium
hemoglobin
isotope
methyl bromide
peptide
trypsin
amino terminal sequence
article
biological monitoring
blood analysis
chemical reaction
controlled study
dilution
environmental exposure
genotoxicity
human
liquid chromatography
mass spectrometry
occupational exposure
priority journal
statistical analysis
Agriculture
Calibration
Chromatography
High Pressure Liquid
Environmental Exposure
Environmental Monitoring
Globins
Hemoglobins
Humans
Hydrocarbons
Brominated
Hydrolysis
Mass Spectrometry
Methylation
Occupational Exposure
Peptides
Reference Standards
Trypsin
Xenobiotics
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/193322
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