Structural Identification of a Polypeptide Biomarker of Phosgene in Human Blood Plasma

Abstract Phosgene is a common intermediate product in large-scale chemical industry with an annual global production volume of approximately 12 million metric tons. At these production volumes, the possibility of phosgene exposure to plant personnel cannot be ruled out; therefore, the chemicoanalytical diagnosis of poisoning, which is complicated by a number of factors, is a problem of considerable current interest. One of the most significant difficulties is the rapid hydrolyzability of phosgene, accompanied by the formation of a number of nonspecific low-molecular-weight products. However, the possibility of the formation of phosgene adducts with human blood proteins, which can serve as characteristic biomarkers of exposure, has been reported previously. In this study, we identified a new polypeptide biomarker of phosgene formed upon accelerated trypsinolysis of blood plasma proteins exposed to phosgene. Using liquid chromatography–high-resolution mass spectrometry (LC–HRMS), we identified the biomarker of phosgene as a trypsin tetrapeptide with the composition ASSAK*QRLK*CASLQK(CO). The limit of detection was about 50 ng/mL on an initial phosgene basis.