Development of a Comprehensive Workflow for Postmortem Insulin Testing in Cases of Suspected Insulin Homicide

Among the greatest remaining challenges for postmortem forensic toxicology laboratories is the detection of toxic peptides in death investigation casework. While this applies to many plant venoms and animal toxins, these cases are infrequent and rarely of criminal nature. The exception is insulin, which has been used in many serial and domestic homicide cases in recent years. No forensic toxicology laboratories in the United States currently offer this testing in biological materials, due to unfamiliarity with protein or peptide analysis, and a lack of reference data for the interpretation of results. The advent of six synthetic insulins has made the detection of these agents even more challenging. These exogenous insulin analogues are designed to have varying pharmacokinetic properties such as long acting, rapid acting, and are used as a replacement for endogenous insulin. When administered in excess or to a person with a functional endocrine system, and particularly to vulnerable populations, the results can be immediately fatal. Currently there are no validated tests available for the forensic investigation of these cases, and insulin homicide cases frequently proceed to trial based on circumstantial or investigative information only. This proposal would refine a validated research assay for seven insulin analogs in vitreous humor as well as C-peptide, develop immunopurification methods to extend the assay to whole blood, and to collect additional biomarker information from actual case populations to assist with interpretation. Once complete, this would represent the first available validated method that can be applied to generate objective data of exogenous insulin administration in suspected criminal cases. This project contains a research and/or development component, as defined in applicable law, and complies with Part 200 Uniform Requirements - 2 CFR 200.210(a)(14). CA/NCF