Acute Butyr-Fentanyl Fatality: A Case Report with Postmortem Concentrations

Journal of Analytical Toxicology, 2016;40:162–166 doi: 10.1093/jat/bkv138 Advance Access Publication Date: 18 December 2015 Case Report Case Report An Acute Butyr-Fentanyl Fatality: A Case Report with Postmortem Concentrations Iain M. McIntyre*, Amber Trochta, Ray D. Gary, Jennifer Wright, and Othon Mena 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: .gov00 Abstract In this case report, we present an evaluation of the distribution of postmortem concentrations of butyr-fentanyl in a fatality attributed principally to the drug. A man who had a history of intravenous drug abuse was found unresponsive on the bathroom floor of his home. Drug paraphernalia was located on the bathroom counter. Toxicology testing, which initially screened positive for fentanyl by enzyme-linked immunosorbent assay, subsequently confirmed butyr-fentanyl, which was then quantitated by gas chromatography–mass spectrometry-specific ion monitoring (GC–MS SIM) analysis following liquid–liquid extraction. The butyr-fentanyl peripheral blood concentration was quantitated at 58 ng/mL compared with the central blood concentration of 97 ng/mL. The liver concentration was 320 ng/g, the vitreous was 40 ng/mL, the urine was 670 ng/mL and the gastric contained 170 mg. Acetyl-fentanyl was also detected in all biological specimens tested. Peripheral blood concentration was quantitated at 38 ng/mL compared with the central blood concentration of 32 ng/mL. The liver concentration was 110 ng/g, the vitreous was 38 ng/mL, the urine was 540 ng/mL and the gastric contained <70 mg. The only other drug detected was a relatively low concentration of benzoylecgonine. The cause of death was certified as acute butyr-fentanyl, acetylfentanyl and cocaine intoxication, and the manner of death was certified as accident. Introduction Butyr-fentanyl (or butyryl-fentanyl; desmethyl-fentanyl) [N-(1phenylethyl)-4-piperidinyl)-N-phenylbutyramide] has been only occasionally encountered as an illicitly used narcotic in the USA. Not currently scheduled in the USA, it is illegal in the UK as it is a modification of fentanyl—by replacement of the N-propionyl group by another acyl group. Like both acetyl-fentanyl and fentanyl, it is a synthetic opioid (Figure 1). As an analgesic, butyr-fentanyl—which has no recognized medical use—has been reported to be ∼10-fold less potent than fentanyl (1). Although the pharmacological effects of butyr-fentanyl have not been specifically investigated clinically in humans, fentanyl-like substances have been generally associated with euphoria, altered mood, drowsiness, miosis, cough suppression, constipation and respiratory depression. There are sparse reports of biological analysis of butyr-fentanyl. As a number of fentanyl analogs demonstrate substantial crossreactivity for the fentanyl antibody on enzyme-linked immunosorbent assay (ELISA) (2, 3), butyr-fentanyl may also be expected to be detected by routine fentanyl screening tests (1). Urinary concentrations from animals intravenously injected with 15 and 45 µg/kg were measured by radioreceptor assay and gas chromatography–mass spectrometry (GC–MS) (4). A multicomponent liquid chromatography– mass spectrometry (LC–MS) procedure has also been utilized for the analysis of serum and urine (1). In a series of four nonfatal intoxications, serum concentrations in two cases were reported at 0.6 and 0.9 ng/mL, and 2.0–65.6 ng/mL was quantitated in the urine of three cases; three of the four cases also reportedly contained fentanyl (1). To date, there have been no accounts of butyr-fentanyl concentrations in an associated fatality, although an overdose resulting in clinically significant hemoptysis, acute lung injury, hypoxic respiratory failure and diffuse alveolar hemorrhage was recently described (5). In this report, for the first time, postmortem concentrations are described for peripheral blood, central blood, liver, vitreous humor, urine and gastric contents in a death certified principally to acute © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: 162 163 Acute Butyr-Fentanyl Fatality (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, positive results were confirmed and quantitated by a subsequent and specific technique. Figure 1. Chemical structures. butyr-fentanyl use. An analytical procedure was developed by minor modification of a GC–MS-specific ion monitoring (SIM) method for fentanyl (6), and recently described for acetyl-fentanyl analysis (7). Methods Case report A 44-year-old man (height 1.70 m and weight 80.2 kg) lived with his wife and daughter. He had spoken with his wife earlier and at that time nothing appeared unusual. Approximately 3 h later that same day, 24 May 2015, she found him unresponsive on the bathroom floor. There was a syringe with plunger on the bathroom counter. A box with drug paraphernalia (used syringes, aluminum foil with black residue, scissors and alcohol wipes) was found elsewhere. 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 heroin abuse and, days later, was supposed to begin an experimental program using slow release Suboxone. A complete autopsy was conducted on 25 May 2015 at 0930 h, ∼18 h after he was found, and documented a single recent puncture site of the left antecubital fossa. The right antecubital fossa and dorsal right forearm had multiple punctate healing scabs. He had evidence of subacute and chronic intravenous drug use in the antecubital fossae, forearms, left wrist and ankles. The lungs were edematous and congested (right 890 g and left 815 g). Microscopically, the lungs also demonstrated edema and congestion, with focal evidence of terminal aspiration of a small amount of gastric content. 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 right 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 a (...truncated)