Can postmortem toxicological findings be influenced by a further release of fentanyl from transdermal patches?–A pilot study using the pig model

Abstract

Due to its high potency, fentanyl is increasingly misused by drug addicts. Yet, interpretation of PM toxicological results is challenging due to different issues leading to falsified higher fentanyl concentrations in blood. On the one hand, fentanyl has a high tendency for PM redistribution (PMR). On the other hand, a PM drug release from applied transdermal patches (TP) can alter blood concentrations. However, the latter has not yet been examined in a controlled manner. Thus, it should be investigated whether fentanyl is released from TP into adipose tissue (AT) or even blood near to or under a TP applied PM. In the context of another study, two fentanyl TP (TP 1: 100 μg/h and TP 2: 25 μg/h) were sticked PM to one pig each. TP 1 was applied to a shaved area on the left shoulder, TP 2 near the right groin. After 24, 48 and 72 h, AT was collected with a distance of approx. 5 (close), 10 (middle) and 15 cm (far) to the patch, respectively. In addition, peripheral blood (PB) and heart blood (HB) were sampled. After 72 hours, the TP was removed and AT was collected under the patch. HB and PB were analyzed after protein precipitation applying a one-point calibration. Regarding AT, quantification of fentanyl was performed after evaporation of the homogenates using a standard addition approach. All extracts were analyzed by LC-MS/MS. Highest fentanyl concentrations were detected in AT collected under the TP after 72 h, with concentrations of approx. 2,700 ng/g (TP 1) and 9,900 ng/g (TP 2). Regarding AT retrieved with a distance to TP 1, fentanyl could be found in every specimen collected after 24 h with highest concentrations of approx. 6.1 ng/g close to the TP, followed by 0.25 (middle) and 0.44 ng/g (far). After 48 h, analysis of AT was only positive for fentanyl in samples collected with a close (0.56 ng/g) and middle (0.19 ng/g) distance to the TP. Applying TP 2, only AT specimen retrieved after 48 were positive for fentanyl. Additionally, fentanyl could be detected in PB drawn after 48 h (0.14 ng/mL) applying TP 2. Screening of HB using patches 1 and 2 went negative for fentanyl. Independent of the dose, fentanyl appears to be released PM from TP into the underlying AT, with higher concentrations applying TP 2 despite a lower fentanyl releasing concentration. This effect might be explained by the respective skin conditions at the application sites, possibly leading to a different permeability of fentanyl. A small amount of the drug is distributed into surrounding AT. Yet, this effect seems to be more pronounced using TP with high releasing concentrations. Additionally, verification of fentanyl in PB could only be obtained after 48 h applying TP 2. The present study shows that fentanyl is released PM from sticked TP. This effect should be considered when interpreting PM findings. In addition, if fentanyl TP are applied chronically, PM blood concentrations of samples collected near to the TP could further be increased due to the subcutaneous fentanyl depot. In future studies, the extent of PMR after an antemortem application of fentanyl TP should be investigated to complement the data on interpretation of PM toxicological findings.