An Acute Acetyl Fentanyl Fatality: A Case Report With Postmortem Concentrations

Journal of Analytical Toxicology 2015;39:490 –494 doi:10.1093/jat/bkv043 Advance Access publication April 26, 2015 Case Report An Acute Acetyl Fentanyl Fatality: A Case Report With Postmortem Concentrations Iain M. McIntyre*, Amber Trochta, Ray D. Gary, Mark Malamatos and Jonathan R. Lucas County of San Diego Medical Examiner’s Office, 5570 Overland Ave., Suite 101, San Diego, CA 92123, USA *Author to whom correspondence should be addressed. Email: Introduction Acetyl fentanyl [N-(1-phenethylpiperidin-4-yl)-N-phenylacetamide] has been encountered as an illicitly used narcotic in the USA since 2013 (1). Acetyl fentanyl and fentanyl are both synthetic opioids, with acetyl fentanyl being the N-acetyl version of fentanyl (Figure 1). As an analgesic, acetyl fentanyl—which has no recognized medical use—has been reported to be 5–15 times more potent than heroin (2), 15 times more than morphine and about 3-fold less potent than that of fentanyl (3). Although the pharmacological effects of acetyl fentanyl have not been specifically investigated clinically in humans (3), fentanyl-like substances have been generally associated with euphoria, altered mood, drowsiness, miosis, cough suppression, constipation and respiratory depression. Typically abused intravenously, acetyl fentanyl has been attributed to 14 deaths in Rhode Island (1), numerous cases in Pennsylvania (4) and 3 deaths in North Carolina (5). Other fatal and nonfatal acetyl fentanyl cases may be mistakenly attributed to heroin because patients present as if experiencing a heroin overdose, and respond similarly (although a larger dose may be required) to treatment with naloxone (6, 7). Despite an increasing frequency of reports, the determination of biological concentrations (antemortem or postmortem) is rare. There are currently no published data, although the acute overdoses from North Carolina evidently exhibited blood and urine concentrations of 330 – 410 ng/mL and 1,000–5,700 ng/mL, respectively (8). As a number of fentanyl analogs demonstrate substantial crossreactivity for the fentanyl antibody on enzyme-linked immunosorbent assay (ELISA) (9, 10), acetyl fentanyl has been detected by routine fentanyl screening tests (1). A liquid chromatography – mass spectrometry (LC – MS) confirmation procedure has been described and utilized for the analysis of urine concentrations following intravenous acetyl fentanyl administration to rats (11). In this report, for the first time, postmortem concentrations are described for peripheral blood, central blood, liver, vitreous humor and urine in a death certified solely to acetyl fentanyl. An analytical procedure was developed by minor modification of a gas chromatography –mass spectrometry (GC – MS) specific ion monitoring (SIM) method for fentanyl analysis (12). Methods Case report A 24-year-old man (height 67 inches and weight 152 pounds) lived at and was the assistant manager of a sober living residence in San Diego. He was visiting his parents’ home for a weekend visit. His parents last saw him at 2030 h on 29 November 2014 when he left to go visit friends. He returned home at an unknown time during the night. At approximately 0850 hours on the morning of 30 November 2014, his mother found him unresponsive behind the closed bedroom closet door with an uncapped syringe with a bent needle, syringe cap and rubber tourniquet. Emergency 9-1-1 was called, and he was declared dead at the scene. The syringe was collected as evidence. He had a history of ‘potential’ heroin abuse. He had previously overdosed twice in the closet at home with what was believed to be heroin. A complete autopsy was conducted on 1 December 2014 at 0945 h, approximately 25 h after he was found, and documented three apparent recent punctures in the left forearm and antecubital fossa. The lungs were edematous and congested (right 610 g and left 580 g). Microscopically, the lungs and a left arm vein contained small amounts of foreign material consistent with chronic/prior intravenous drug abuse. There were no other significant findings. Postmortem specimen collection All specimens analyzed were collected at autopsy at the San Diego County Medical Examiner’s Office. Peripheral blood (20 mL) was drawn from the left common iliac vein (blood returning from the leg and visually identified in the pelvis at autopsy) and stored in standard glass tubes containing sodium fluoride (100 mg) and potassium oxalate (20 mg). Central blood was collected directly from the heart and placed in identical tubes. Sections of the right lobe of liver were collected and stored in an opaque plastic four ounce container without preservative. Vitreous humor samples were withdrawn from the eyes with a syringe and stored in a glass tube without preservative. Urine was collected into in an opaque plastic four ounce container without preservative. All samples were stored at 48C until analyzed within 6 weeks of collection. Toxicology A comprehensive toxicological screening regimen was performed. Postmortem blood was screened for alcohol and volatile # The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: In this case report, we present an evaluation of the distribution of postmortem concentrations of acetyl fentanyl in a fatality attributed to the drug. A young man who had a history of heroin abuse was found deceased at his parents’ home. Toxicology testing, which initially screened positive for fentanyl by ELISA, subsequently confirmed acetyl fentanyl by gas chromatography– mass spectrometry specific ion monitoring (GC–MS SIM) analysis following liquid –liquid extraction. No other drugs or medications, including fentanyl, were detected. The acetyl fentanyl peripheral blood concentration was quantified at 260 ng/mL compared with the central blood concentration of 250 ng/mL. The liver concentration was 1,000 ng/kg, the vitreous was 240 ng/mL and the urine was 2,600 ng/mL. The cause of death was certified due to acute acetyl fentanyl intoxication, and the manner of death was certified as an accident. compounds (GC-FID headspace), 12 drugs of abuse panel by ELISA (cocaine metabolite, opiates, methamphetamine, benzodiazepines, cannabinoids, fentanyl, phencyclidine, oxycodone, methadone, zolpidem, carisoprodol and buprenorphine; Immunalysis, Inc., Pomona, CA, USA), an alkaline drug screen by GC –MS following solid-phase extraction and an acid/neutral drug screen with HPLC-photodiode array detection following specimen precipitation with acetonitrile. An additional screen (GC– MS) was also performed on the syringe exhibit that was collected from the scene. Following routine practice, the positive result was confirmed and quantified by a subsequent and specific technique. Acetyl fentanyl confirmation analysis Materials All solvents and chemicals were purchased from Fisher Scientific (Pittsburgh, PA, USA) and were analytical grade or better. Test tubes made of borosilicate glass used for all phases of (...truncated)