The project anticipated that such tools would enable drug exposure assessment for these compounds over a longer period of time than is currently possible, as well as provide an alternative or complement to the customary hair analysis. A potential technology for longer term monitoring of drug exposure involves the measurement of the products of covalent modification of free moleties of blood proteins, such as hemoglobin (Hb) and serum albumin (SA) by reactive metabolites (RM) of drugs. Since they typically persist for the life of the protein, such protein "adducts" can provide a much longer period for detection of exposure to drugs than is generally possible by direct measurement of parent compound or a metabolite. Although widely used in human exposure assessment for environmental and occupational chemicals, applications of protein adducts as markers of illicit drug exposure are virtually nonexistent. The current project's preliminary studies demonstrate that in vitro modification of glutathione (GSH) and model thiol that contains peptides by RM of certain abused drugs is potentially feasible as a means of identifying drug exposure over a longer period of time since exposure. This report advises that this project has made a key step toward developing a useful drug monitoring strategy based on blood protein modification that will lead to the next stage, which will involve the development and validation of a practical assay. Implications of these project results are drawn for criminal justice policy and practice in the United States. 18 figures, 4 tables, and a listing of presentations and publications of project results
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