Superiority of postmortem liver fentanyl concentrations over peripheral blood influenced by postmortem interval for determination of fentanyl toxicity

Objective: The current study was undertaken to determine the relationship between postmortem (PM) peripheral blood (PB) and liver fentanyl concentrations and the role of measuring liver fentanyl concentrations in cause of death investigations in medical examiner cases in which fentanyl was identified.

Design and methods: FB and liver tissue were routinely collected at autopsy from 4 Minnesota medical examiners' offices in 2010-2011. Samples were analyzed by gas chromatography-mass spectrometry (GC-MS).

Results: PB fentanyl ranged from <2-15μg/L in non-drug related deaths (n=5), <2-22μg/L from mixed drug toxicity (n=26) and 3.7-56μg/L from fentanyl toxicity (n=33). Liver fentanyl ranged from 11 to 104μg/kg, 6 to 235μg/kg, and 18 to 365μg/kg, respectively. PB and liver fentanyl showed a modest correlation (r=0.67). PM interval to the liver/blood ratio showed a decreasing ratio over increasing PM interval in cases from fentanyl and mixed drug toxicity. Liver fentanyl concentrations best define therapeutic use at <23μg/kg and fatal toxicity at >56μg/kg, without substantial overlap as found in blood fentanyl concentrations.

Conclusion: Discriminatory liver fentanyl concentrations suggestive of therapeutic or toxic drug levels may better assist cause of death determination in cases of suspected fentanyl toxicity than postmortem PB concentrations. Peripheral blood fentanyl concentrations appear to undergo postmortem redistribution, associated with an increasing PM interval.