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For the past 60 years, benzodiazepines such as chlordiazepoxide, diazepam, and alprazolam have been used as pharmaceutical medications for the treatment of myriad conditions including anxiety, seizures, and insomnia. In more recent years, novel benzodiazepine derivatives have emerged as illicit substances in powders and counterfeit tablets on the illicit drug market. In 2016, bromazolam, a brominated derivative of alprazolam, emerged on the illicit drug market in Europe, but the substance was not reported in the USA until 2019-2020. In this study, we report the emergence and subsequent prevalence of bromazolam in postmortem blood in the state of Indiana during 2023. Analysis was completed by a solvent protein precipitation extraction with acetonitrile and detection by liquid chromatography with quadrupole time of flight mass spectrometry. During 2023, bromazolam was detected in 94 cases across 25 counties in Indiana. It was never the sole substance detected and was commonly detected alongside fentanyl (83 cases), norfentanyl (77 cases), 4-anilino-N-phenethylpiperidine (76 cases), acetylfentanyl (49 cases), methamphetamine (32 cases), naloxone (25 cases), 11-nor-9-carboxy-tetrahydrocannabinol (24 cases), and benzoylecgonine (20 cases). After official query with the Indiana Department of Health, it was found that bromazolam was specifically included in the cause of death certification in 31 fatalities (32.9%). Due to the scarcity of information regarding this novel benzodiazepine derivative in postmortem toxicology and its involvement in fatalities, it is important that forensic toxicology laboratories consider adding bromazolam to their comprehensive scope of analysis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Mitragyna speciosa, a species of plant that is native to Thailand, Malaysia and Southeast Asia, contains two major psychoactive alkaloids: mitragynine and 7-hydroxymitragynine. Pharmacologically, the alkaloids exhibit biphasic effects-at low doses, stimulant effects are realized, while high doses exhibit sedative effects. For years, the plant has been used recreationally and medicinally for these effects, but its use has been implicated in and associated with intoxications and deaths. In this case report, we describe two cases whereby decedents presented with single-substance fatal intoxications by mitragynine in the absence of other postmortem toxicological findings. The cases entail young male decedents in outdoor settings (e.g., driving a vehicle and bicycle). Postmortem blood concentrations were 2,325 and 3,809 ng/mL. The medical examiner certified the cause of death as acute mitragynine intoxication in both cases. The toxicology results presented become useful when considering mitragynine to be the offending agent in lethal single-drug intoxications; further, the information included is pertinent to medical examiners, forensic pathologists, forensic toxicologists and emergency department personnel in evaluating possible poisoning and lethality by mitragynine., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Fentanyl analogs pose a unique challenge for forensic pathologists and toxicologists. The extreme potency of these analogs results in minute blood, urine and vitreous concentrations that are technically difficult to identify. This in addition to their absence from standard drug screening may potentiate a setting of apparent drug overdose without an immediately identifiable source. The following case series illustrates three such encounters with acrylfentanyl, an analog whose presence has not yet been reported in the scientific literature in the United States. In case 1, a 23-year-old male with a history of heroin abuse was found unresponsive in a field several feet away from his parked vehicle. Drugs and paraphernalia recovered from the vehicle tested positive for methamphetamine and acrylfentanyl. Directed toxicology was requested, revealing acrylfentanyl concentrations of 0.3 ng/mL. In case 2, a 43-year-old male with a history of heroin abuse was found unresponsive in his home after allegedly injecting what he thought to be heroin. Directed toxicology revealed an acrylfentanyl concentration of 0.95 ng/mL in peripheral blood. In case 3, a 26-year-old male with a history of heroin abuse use found unresponsive on the bathroom floor of a grocery store. Drug paraphernalia and a plastic baggy with residue were present. Directed analysis of peripheral blood for fentanyl analogs revealed acrylfentanyl and furanylfentanyl at concentrations of 0.32 and 0.95 ng/mL, respectively. In all three cases, the initial comprehensive blood toxicology did not reveal the presence of acrylfentanyl, highlighting the need for directed testing when scene findings and history suggest a possible substance outside the scope of traditional screening.

Carfentanil is a mu (μ) opioid receptor agonist and is estimated to be ~10,000 times more potent than morphine in animal (non-human) models. It is not approved for human use and is only used to immobilize large exotic animals in veterinary medicine. In mid-2016, carfentanil emerged as a contaminant in street heroin in the USA and was central to a large number of emergency department visits and deaths. We describe an analytical method for the detection and quantification of carfentanil in whole blood specimens via a protein precipitation extraction with acetonitrile and liquid chromatography with triple quadrupole mass spectrometry. From 1 September 2016 to 1 January 2017, carfentanil was identified in 262 postmortem blood specimens. Blood concentrations ranged from 10.2 to 2,000 ng/L, with a mean concentration equal to 193 ng/L and a median concentration equal to 98.4 ng/L. We describe 13 fatalities from the Midwest region (Indiana, Kentucky, Michigan and Ohio) of the USA in which our laboratory performed comprehensive toxicology and in which carfentanil was detected and associated with cause of death. We recommend that any analytical method applied to the detection of this substance in human whole blood specimens be sufficiently sensitive to detect sub-100 ng/L concentrations and preferably utilize a 10-50 ng/L reporting limit., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The use of synthetic cannabinoids and related products has been associated with adverse effects including seizure, acute kidney injury, and sudden death. We report the death of an individual that was associated with the synthetic cannabinoid 5F-AMB. Specimens were extracted via a liquid-liquid extraction at pH 10.2 into hexane:ethyl acetate. Analysis was completed via liquid chromatography tandem mass spectrometry. For this case report, we briefly describe the extraction and instrumental methods for 5F-AMB as well as the blood toxicology results (5F-AMB, 0.3ng/mL) and case circumstances and autopsy findings. Cause and manner of death was certified as accidental death due to synthetic cannabinoid toxicity. We also briefly review any previously published reports in which 5F-AMB was analytically confirmed and determined to be involved with cause of death., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Over the last few years, NBOMe substances have been used either as a legal alternative to lysergic acid diethylamide (LSD) or sold surreptitiously as LSD to unknown users. These NBOMe substances have been detected in blotter papers, powders, capsules and liquids. We report the deaths of two teenage male subjects that were related to 25B-NBOMe and 25I-NBOMe in Indiana during 2014. Samples were extracted via a solvent protein precipitation with acetonitrile and analyzed via ultra-performance liquid chromatography with tandem mass spectrometry. For these two cases, we describe the NBOMe instrumental analysis, toxicological results for postmortem heart blood and urine specimens and the relevant case history and pathological findings at autopsy. In the first case, 25B-NBOMe was detected in postmortem heart blood at 1.59 ng/mL; in the second case, 25I-NBOMe was detected in postmortem heart blood at 19.8 ng/mL. We also review relevant published casework from clinical toxicology and postmortem toxicology in which analytically confirmed 25B-NBOMe and 25I-NBOMe were determined to be causative agents in intoxications or deaths., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Synthetic cannabinoids are a group of compounds that are structurally diverse and are commonly found in various herbal incense and potpourri blends, which are sold in convenience stores, smoke shops and over the Internet. During the past few years, multiple state and federal legislations have been enacted controlling various subsets of these compounds that have been detected in compound categories generally considered the first and second product generations. As shown in previous studies, as compounds become controlled, new compounds emerge and become prevalent. We report on the emergence and prevalence of five different compounds (A796,260, MAM-2201, UR-144, URB597 and XLR-11) in the state of Indiana through their qualitative detection in solid-dosage herbal products via rapid solvent extraction and ultra-performance liquid chromatography with time-of-flight mass spectrometry (UPLC/ToF). We demonstrate the use of UPLC/ToF to be a suitable tool in the identification of these substances in a crime laboratory or forensic laboratory setting, which ultimately enables a laboratory to design assays for the detection of specific analytes in biological specimens in regard to regional trends and prevalence.

Objectives: Methadone-related overdose deaths increased in the United States by 468% from 1999 to 2005. Current studies associate the nonmedical use of methadone with methadone-related deaths. This study describes medical examiner cases in rural Virginia in 2004 with methadone identified by toxicology and compares cases according to source of methadone., Methods: In 2004, all intentional and unintentional poisoning deaths from the Office of The Chief Medical Examiner, Western District of Virginia, were reviewed to identify cases in which methadone was a direct or contributing cause of death. The Virginia Prescription Monitoring Program was reviewed for prescription opioids in the name of these identified decedents. Decedent participation in local opioid treatment programs (OTP) was also assessed., Results: The source of methadone in the 61 methadone-related overdose deaths was mostly nonprescribed (67%), although 28% of decedents were prescribed methadone for analgesia. Only 5% of decedents were actively enrolled in an OTP. The majority of deaths were attributed to polysubstance overdose., Conclusions: The majority of methadone overdose deaths in this study were related to illicit methadone use, rather than prescribed or OTP uses. Interventions to decrease methadone-related deaths should focus on reduction of nonprescription use of methadone.

Fatalities associated with fentanyl hydrochloride are increasingly seen in Massachusetts. Between September 2005 and November 2006, 5009 medicolegal investigations associated 107 deaths with licit or illicit fentanyl use, along with a co-detection of an opiate/opioid or cocaine/benzoylecognine, or both. Deaths associated with illicit fentanyl use occur in younger people (39.4 vs. 61.5 years) with higher fentanyl (17.1 ng/mL vs. 4.4 ng/mL) and lower morphine (76.9 ng/mL vs. 284.2 ng/mL) postmortem blood concentrations, and more frequent cocaine co-intoxication (65% vs. 3%), than deaths associated with illicit fentanyl use. A wide range of postmortem blood concentrations of fentanyl was detected (trace-280 ng/mL), with a minimum concentration of 7 ng/mL of fentanyl strongly associated with illicit use of fentanyl in poly-drug cases. The most commonly detected opiates/opioids in illicit fentanyl users were: morphine (29%), oxycodone (14.5%), and methadone (14.5%). Ethanol, cannabinoids, diazepam, citalopram, and diphenhydramine were each detected in greater than 10% of the licit fentanyl cases. Most fentanyl abusers died at their own home and their deaths were most often classified as accidental. Mapping of primary residences of decedents revealed conspicuous clustering of the illicit fentanyl use cases, as opposed to the random pattern in licit use cases. Fentanyl misuse is a public health problem in Massachusetts.

The effects of antemortem ingestion of ethanol by domestic pigs, Sus scrofa L., on postmortem insect successional patterns and the development of Phormia regina (Meigen) were studied during summer 2003 in Blacksburg, VA. Insect samples were collected from the carcasses of ethanol-treated and untreated pigs for 10 d postmortem during two successional studies. In total, 32 insect taxa were collected during the two studies, with 29 and 27 taxa observed on the carcasses of ethanol-treated and untreated pigs, respectively. The earliest arrivers to both carcass types were dipterans. This group was represented by six families, with P. regina and Phaenicia coeruleiviridis (Macquart) being the most common calliphorids. Beetles in six families were collected on the carcasses of ethanol-treated pigs, but only three of the families were collected on carcasses of the untreated pigs. Permutation analyses to test the null hypothesis of no similarity between successional patterns of insect taxa from carcasses of ethanol-treated and untreated pigs showed that the successional patterns were similar between carcass types in the first (P = 0.003) and the second (P = 0.01) studies. The results of the development study of P. regina maggots in the field show that there was a significant difference between the distributions of length for maggots reared on loin tissue from ethanol-treated and untreated pigs. Maggots that fed on tissue from ethanol-treated pigs took approximately 11.9 h longer to reach the pupal stage than maggots that fed on tissue from untreated pigs. The longer developmental time for maggots on tissue from ethanol-treated pigs was due mainly to the longer postfeeding period of the third instar.

We report the rapidly increasing finding of fentanyl in medical examiner cases in southwestern Virginia. During the past 3 years, fentanyl cases have increased from 3 in 2000 to 12 in 2002. The first medical examiner case of 2003 was a fentanyl poisoning. Nineteen of 23 cases were attributed to fentanyl misuse or abuse of fentanyl transdermal patches. Routes of administration were transdermal, transmucosal/oral, intravenous, and combinations of routes of administration. Fentanyl was identified using a solid-phase extraction basic drug screen in blood and/or urine followed by full scan gas chromatography-mass spectrometry (GC-MS) in the electron impact ionization mode. Fentanyl quantitation was performed using selected ion monitoring GC-MS. The method was linear from 1 to 50 microg/L with a limit of quantitation of 1 microg/L. Fentanyl blood concentrations ranged from 2 to 48 microg/L with a mean concentration of 18 microg/L. The age range of the decedents was 16-53 with an average age of 37. Southwestern Virginia is currently a "hot spot" for misuse and abuse of oxycodone and methadone. The rapid rise in the number of fentanyl cases over the past three years, the increasing availability of fentanyl patches, and the large number of case histories indicating misuse or abuse suggest that fentanyl is rapidly becoming an additional desired opioid similar to oxycodone and methadone.

This toxicology update reviews the oxidative stress metabolites of catecholamines, postulated to be the biochemical initiators of cardiotoxicity. A brief overview of catecholamine metabolism is provided with several noteworthy historical observations relating to the autoxidation and rearrangement of epinephrine. The basic chemical and physical properties of adrenochrome and adrenolutin are discussed. The autoxidative, enzymatic and cellular basis for the transformation of catecholamines to oxidative metabolites is reviewed. Mechanisms seeking to account for the observed cardiotoxic changes in isolated heart perfusion studies and in vivo models are described., (Copyright 2001 John Wiley & Sons, Ltd.)