Methods for Retrospective Detection of Exposure to Toxic Scheduled Chemicals. Part B: Mass Spectrometric and Immunochemical Analysis of Covalent Adducts to Proteins and DNA

In this article, an overview of themethods that are currently available for retrospective detection of exposure to a number of chemical warfare agents (CWA), based on adducts formed with macromolecules such as proteins, is presented. These methods can be applied for various purposes, e.g. diagnosis and dosimetry of exposure of casualties, confirmation of nonexposure, verification of nonadherence to the Chemical Weapons Convention, health surveillance, and forensic purposes. The advantage of using protein adducts as biomarkers in comparison with free metabolites is that they are potentially much more longlived. The methods are predominantly based on LC/MS analysis of enzymatic digests of the (modified) proteins or on selective removal of the specific adduct moiety from the protein, followed by GC/MS or LC/MS. Several of the methods have been successfully applied to actual cases and were shown to be highly retrospective.