Low Level Exposure to Sulfur Mustard: Development of a SOP for Analysis of Albumin Adducts and of a System for Non-Invasive Diagnosis on Skin

摘要

The research described in this report is focused on the development of methods for diagnosis of exposure to chemical agents. In Volume I, the development of a Standard Operating Procedure (SOP) for diagnosis of exposure to sulfur mustard is described, based on mass spectrometric analysis of the sulfur mustard-adducted tripeptide (S-(2-hydroxylethylthi oethyl)-Cys-Pro-Phe), derived from albumin. The SOP for the tripeptide adduct was successfully demonstrated to a scientist of USAMRICD. The method could be set up within one day and the scientist of USAMRICD was able to perform the entire assay on his own after 2 days. Furthermore, in Volume I the mass spectrometric analysis of histidine sulfur mustard adducts is extensively described, as well as an immunoslotblot assay for detection of sulfur mustard adducts to keratin. In Volume II (addendum), it is described how several methods for diagnosis of exposure to chemical agents (sulfur mustard, Lewisite, phosgene, nerve agents) have been improved or developed and subsequently transferred to Centers for Disease Control & Prevention. Furthermore, within this context a generic method for detection of covalently modified human butyrylcholinesterase has been developed, in order to circumvent the shortcomings of the current (specific) assays for diagnosis of exposure to OP-anticholinesterases. Finally, various reference compounds have been synthesized and delivered to CDC.