Print Email Facebook Twitter In vitro adduct formation of phosgene with albumin and hemoglobin in human blood Title In vitro adduct formation of phosgene with albumin and hemoglobin in human blood Author Noort, D. Hulst, A.G. Fidder, A. van Gurp, R.A. de Jong, L.P.A. Benschop, H.P. Prins Maurits Laboratorium TNO Publication year 2000 Abstract The development of procedures for retrospective detection and quantitation of exposure to phosgene, based on adducts to hemoglobin and albumin, is described. Upon incubation of human blood with [14C]phosgene (0-750 μM), a significant part of radioactivity (0-13%) became associated with globin and albumin. Upon Pronase digestion of globin, one of the adducts was identified as the pentapeptide O=C-(V-L)-S-P-A, representing amino acid residues 1-5 of α-globin, with a hydantoin function between N-terminal valine and leucine. Micro-LC/tandem MS analyses of tryptic as well as V8 protease digests identified one of the adducts to albumin as a urea resulting from intramolecular bridging of lysine residues 195 and 199. The adducted tryptic fragment could be sensitively analyzed by means of micro-LC/tandem MS with multiple-reaction monitoring (MRM), enabling the detection in human blood of an in vitro exposure level of ≥ 1 μM phosgene. Subject ToxicologyAlbuminsAlpha globinAmino acid sequenceEnvironmental exposureHumansProtein analysisProtein bindingProtein blood levelProtein determinationProtein synthesisRadioactivityChromatography, High Pressure LiquidEnvironmental monitoringHemoglobinsMass SpectrometryPhosgeneProtein BindingHemoglobinsPhosgene, 75-44-5 To reference this document use: http://resolver.tudelft.nl/uuid:1d70da18-8c3a-438f-bd5c-5d635b9dab90 DOI https://doi.org/10.1021/tx000022z TNO identifier 235658 ISSN 0893-228X Source Chemical Research in Toxicology, 13 (8), 719-726 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.