title: LC-MS/MS analysis of fentanyl and norfentanyl in a fatality due to application of multiple Durogesic transdermal therapeutic systems.
abstract: 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 microg/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 microg/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 microg/L (3.0 microg/L) in right and 28.2 microg/L (3.5 microg/L) in left subclavian blood, 21.3 microg/L (<2 microg/L) in right and 20.9 microg/L (<2 microg/L) in left femoral blood, 37.6 microg/L (4.2 microg/L) in right and 33.9 microg/L (4.4 microg/L) in left ventricular blood, 282.9 microg/L (121.2 microg/L) in urine, 688.2 microg/L in stomach contents, 122.5 microg/L (25.4 microg/L) in bile, 19.5 microg/L (< 2 microg/L) in vitreous humour, 203.0 microg/kg (26.6 microg/kg) in liver and 78.6 microg/kg (46.3 microg/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.
authors.affiliation: Department of Analytical Toxicology, Chemiphar N.V., Lieven Bauwensstraat 4, B-8200 Bruges, Belgium.
authors.forename: Vera
authors.initials: V
authors.lastname: Coopman
authors.forename: Jan
authors.initials: J
authors.lastname: Cordonnier
authors.forename: Karen
authors.initials: K
authors.lastname: Pien
authors.forename: Dirk
authors.initials: D
authors.lastname: Van Varenbergh
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000032:analysis / Q000506:poisoning*; D001646:Bile / Q000737:chemistry; D002853:Chromatography, Liquid; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000032:analysis / Q000506:poisoning*; D053593:Forensic Toxicology; D005766:Gastrointestinal Contents / Q000737:chemistry; D006801:Humans; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D009369:Neoplasms / Q000150:complications; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D021241:Spectrometry, Mass, Electrospray Ionization; D013405:Suicide; D014822:Vitreous Body / Q000737:chemistry
chemical_list: D000701:Analgesics, Opioid; C080127:norfentanyl; D005283:Fentanyl