Novel Blood Protein Modification Assay for Retrospective Detection of Drug Exposure

As submitted by the applicant: Detection and confirmation of drug exposure typically relies on measurement of parent compounds or metabolites in blood or urine. However, this approach has significant drawbacks with regard to the useful time frame for drug detection, since most drugs and their metabolites are cleared from the body within a week. Consequently, such measurements alone cannot provide data on past episodic or repeated exposure. Nevertheless, longer windows of detection are valuable for measurement of drug compliance or abstinence, such as in pain drug management, drug addiction rehabilitation programs, and probation/parole criminal justice situations. Currently, retrospective assessment of drug use is limited to analysis of hair. While clearly important for this purpose, hair analysis does have certain technical and interpretive challenges. Another potential technology for longer-term drug monitoring involves measurement of the products of covalent modification (i.e., "adducts") of the blood proteins hemoglobin (Hb) and serum albumin (SA) by reactive drug metabolites. Since they persist for the life of the protein, such modifications can provide a considerably longer window of detection than is possible with parent drugs or metabolites. While widely used in exposure assessment for environmental and occupational chemicals, applications of protein adducts as markers of illicit drug exposure are virtually nonexistent.

This project contains a research and/or development component, as defined in applicable law.

ca/ncf