No. A group comparison showing substantially higher postmortem fentanyl concentrations does not provide a factor for reconstructing an individual’s concentration during life. Andresen and colleagues compared separate postmortem and living-patient groups receiving transdermal fentanyl. They did not measure paired before-and-after concentrations in the same people.
Which people and specimens were compared?
The publication describes a postmortem comparison of 118 cases and serum from 27 living pain-treatment patients. Analyses used smaller subsets because of undetectable concentrations, defective patches or other exclusions. The postmortem group was predominantly elderly and medically ill; 63% had fentanyl prescribed for oncological pain.
Deaths were initially considered unrelated to fentanyl after medical-history review and examinations by two physicians. No routine autopsy was performed in that comparison cohort. One case was retrospectively excluded after suspicion of fentanyl intoxication arose. The authors acknowledged that a contributory role of fentanyl could not be completely excluded in the remaining cases.
Postmortem whole blood came from the femoral vein after dissection and visual localization. Samples were collected one to 41 days after death and stored without preservative at −20°C. Living-patient serum was collected at least 24 hours after application of a new patch, following at least one week of therapy, and stored at 4–8°C. All study specimens were analyzed within three months.
How reliable were the measurements?
Fentanyl was quantified by liquid chromatography–mass spectrometry using fentanyl-d5 as internal standard. The detection limit was 0.9 µg/L and quantification limit 1.0 µg/L. Initial calibration covered 1–15 µg/L, with an extended curve for higher results. Inter- and intra-day imprecision was below 15%; recovery was 84.6% at 2.5 µg/L and 93.7% at 10 µg/L.
The reported concentrations are in micrograms per liter, not milligrams per liter. Quality controls showed no loss outside the study’s accepted variation during three-month temperature comparisons. That control experiment does not independently establish stability under every authentic specimen’s handling history.
What “up to nine times higher” meant
The authors described dose-dependent group-average differences of approximately four- to ninefold between postmortem blood and living-person serum. These were comparisons across different people, specimen types, illnesses and collection times. They were not observed within-person increases caused solely by death.
The 102 measurable postmortem cases with intact patches used in one regression showed a dose–concentration correlation of r = 0.596. Restricting the analysis to doses up to 150 µg/hour reduced it to r = 0.286 in 98 cases, although that association remained statistically significant. In the living group, the dose regression included only 12 of 27 patients with quantifiable, eligible results and gave r = 0.742.
Those findings do not support predicting an individual’s concentration from patch strength. Nor does statistical significance make the smaller postmortem association a useful reconstruction equation.
What the study could not separate
Postmortem redistribution was a plausible explanation for higher concentrations, but the study did not isolate it from differences between the patient groups. Whole blood and serum were also different matrices, even though the authors discussed literature suggesting similar fentanyl partitioning during life.
Physical-build categories did not show a significant concentration difference at the two patch doses examined. Longer postmortem intervals did not inevitably produce higher concentrations. Because the earliest collection was one day after death, the study could not directly investigate the first postmortem hours.
The authors found substantial overlap between concentrations associated with therapeutic administration and reported intoxications. A measured fentanyl concentration alone therefore did not establish impairment or cause of death. Medical history, tolerance, co-medication, patch history and specimen details remained necessary.
Compare the separate problem of hospital versus autopsy cannabinoid measurements. A group comparison and a within-person comparison support different inferences.
Primary source
Andresen H, Gullans A, Veselinovic M, et al. Fentanyl: Toxic or Therapeutic? Postmortem and Antemortem Blood Concentrations After Transdermal Fentanyl Application. Journal of Analytical Toxicology. 2012;36(3):182–194. doi:10.1093/jat/bks005.
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