Postmortem blood methadone concentrations

Cases of high methadone concentrations in postmortem blood often are at risk of misinterpretation. In living individuals, a patient’s extreme tolerance and high/frequent doses may lead to antemortem blood methadone concentrations above 500 ng/mL. After death, interpretation is further complicated by postmortem redistribution, specimen selection and other factors.

Three major issues that may work together to create a somewhat confusing picture are 1) significant overlap between published therapeutic, toxic and lethal concentrations, 2) incomplete or missing case history, and 3) postmortem redistribution (PMR). According to Winek (1), therapeutic, toxic and lethal blood methadone concentrations are 75-1100, 200-2000, and 400-1800 ng/mL, respectively. Clearly, without a medical history or other investigative information, determining cause of death from these levels, or drawing any conclusions about drug effects, is not possible. Therefore, a reliable case history is essential to provide important information about dosing and possibly even antemortem blood concentrations (e.g., hospital specimens). However, even with this information, the likelihood of PMR must also be considered. Heart/peripheral blood concentrations ratios in 100 cases (2) were 0.5-9.5. Thus, a antemortem concentration of 1000 ng/mL (potentially therapeutic), could result in a postmortem heart blood concentration more than 5000 ng/mL.

The medico-legal issues surrounding these phenomena can be very complex. A complete investigation should include law enforcement, pathology and toxicology. When available, the decedent’s medical history also may provide essential information regarding drug use and/or prescription regimen. However, if only toxicological data are available, assumptions about the cause of death or drug effects (e.g., psychomotor impairment) prior to death should be avoided.

1. C.L. Winek, W.W. Wahba, C.L. Winek Jr., T.W. Balzer, Drug and Chemical blood-level data 2001, Forensic Sci. Int. 122 (2001) 107-123.

2. J.A. Jennings, R.A. Jufer, R.T. Callery, R. Pretzler. Distribution of methadone and EDDP in 100 postmortem cases. Society of Forensic Toxicologists, Nashville, TN, Oct 19-20, 2005.