LC–MS/MS analysis of fentanyl and norfentanyl in a fatality due to application of multiple Durogesic® transdermal therapeutic systems

Fentanyl is a potent synthetic narcotic analgesic administered in the form of a transdermal patch for the management of chronic pain. A 78-year-old woman with a history of cancer was found dead in bed. She was lying on her back. The external examination revealed 10 Durogesic® transdermal therapeutic systems (100 μg/h fentanyl) on the body.Liquid–liquid extraction and liquid chromatography tandem mass spectrometry with electrospray source in positive ionization mode was applied for the quantitation of fentanyl and its major metabolite norfentanyl in the post-mortem samples. Fentanyl-d5 and norfentanyl-d5 were used as internal standards. Multiple reaction monitoring was used for specific detection. Calibration was performed by addition of standard solutions to drug-free matrix (blood, urine and liver) prior to extraction. The method showed good linearity for fentanyl and norfentanyl over a concentration range of 5–150 μg/L in reconstituted extracts with coefficients of determination equal or greater than 0.998. Percent mean within-day precision and accuracy of 0.9–1.0% and 99.4–101.1% for fentanyl and 2.0–4.5% and 93.1–101.0% for norfentanyl were obtained.Mean extraction recoveries varied between 95.5% and 100.3% for fentanyl and 39.2–57.4% for norfentanyl. The following fentanyl (norfentanyl) concentration in the post-mortem samples were measured; 28.6 μg/L (3.0 μg/L) in right and 28.2 μg/L (3.5 μg/L) in left subclavian blood, 21.3 μg/L (<2 μg/L) in right and 20.9 μg/L (<2 μg/L) in left femoral blood, 37.6 μg/L (4.2 μg/L) in right and 33.9 μg/L (4.4 μg/L) in left ventricular blood, 282.9 μg/L (121.2 μg/L) in urine, 688.2 μg/L in stomach contents, 122.5 μg/L (25.4 μg/L) in bile, 19.5 μg/L (< 2 μg/L) in vitreous humour, 203.0 μg/kg (26.6 μg/kg) in liver and 78.6 μg/kg (46.3 μg/kg) in kidney. We concluded that the woman's death was caused by acute intoxication with fentanyl. The manner of death was presumed to be suicide due to excessive administered Durogesic® transdermal therapeutic systems.