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

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 fur 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 wed established monitoring of N-terminal adducts, the latter not being applicable to all alkylating agents