Finding no fentanyl above an assay’s detection limit did not establish absence of documented patch treatment. In a prescribed-transdermal-fentanyl study, 14 postmortem blood specimens were below the reported 0.9 µg/L detection limit despite patches being present. The result was a qualified analytical finding, not a measured concentration of zero.
Who was included?
Andresen and colleagues described a postmortem comparison of 118 cases and a separate group of 27 living pain-treatment patients. Deceased participants were identified during examinations before cremation when fentanyl patches were found and death was considered unrelated to overdose. Medical or hospital records were used to corroborate the patch dose.
The postmortem group was predominantly elderly and medically ill. Two physicians assessed the circumstances, but routine autopsy was not performed in the comparison cohort. One case was retrospectively excluded after suspicion of fentanyl intoxication led to further investigation. A contributory role of fentanyl could not be completely excluded in the remaining cases.
How was the postmortem specimen obtained?
Whole blood was collected from the femoral vein after anatomical dissection and visual localization. The vein below the needle was massaged to facilitate collection. Sampling occurred one to 41 days after death. Specimens were stored without preservative at −20°C and analyzed within three months.
This was not a controlled experiment assigning equal exposure and sampling every participant at a fixed interval. The documented patch and treatment history addressed exposure, while the laboratory result addressed the collected specimen under its measurement conditions.
What did “below detection” mean?
The LC–MS method used fentanyl-d5 as an internal standard. Its reported detection limit was 0.9 µg/L and quantification limit 1.0 µg/L. Initial calibration covered 1–15 µg/L, with an extended calibration for higher concentrations. Inter-day and intra-day imprecision were below 15%; recovery was 84.6% at 2.5 µg/L and 93.7% at 10 µg/L.
A below-detection result meant that the method did not detect fentanyl above that boundary. It did not identify an exact subthreshold concentration. The limits are in micrograms per liter, numerically equivalent to nanograms per milliliter, not milligrams per liter.
These were findings from a fentanyl-specific mass-spectrometric procedure. They should not be confused with a negative general opiate immunoassay that might not adequately target fentanyl.
Did recent patch application explain every negative result?
The authors described application shortly before death in several below-detection cases, including five with patches applied within a few hours to one day before death and another after two days of treatment. Low patch strengths also featured in their discussion of possible explanations.
However, they could not explain two other below-detection cases with patch doses of 75 and 125 µg/hour and recorded treatment lasting more than ten months. These unexplained observations did not demonstrate assay failure, treatment nonadherence or a particular postmortem process. The study did not resolve which explanation applied.
Living-patient results were a separate comparison
Fourteen of the 27 living patients also had serum concentrations below detection. They had received patch therapy for at least a week, and serum was collected at least 24 hours after a new patch was applied. These were different people and a different matrix from the postmortem group.
The two sets of negative findings therefore were not paired evidence that a person’s fentanyl disappeared after death. They also did not estimate the sensitivity of every modern fentanyl assay or a universal probability of detection during prescribed therapy.
How should a negative finding be interpreted?
Keep the actual assay limit, specimen site, patch history and collection interval attached to the result. Do not substitute zero for an unmeasured concentration or infer absence of prior exposure solely from this negative finding. Conversely, the presence of a patch does not itself establish impairment or fentanyl as the cause of death.
For the distinct problem of a broader screen that misses the target, see why an opiate screen could miss fentanyl.
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;36:182–194. doi:10.1093/jat/bks005.
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