George Behonick

Four postmortem case reports with quantitative detection of the synthetic cannabinoid, 5F-PB-22.

In January 2014, the US government temporarily designated 5F-PB-22, along with three other synthetic cannabinoids (AB-FUBINACA, ADB-PINACA and PB-22), into Schedule I. Over the course of a 4-month time period (July-October 2013), our laboratory quantitatively identified 5F-PB-22 in specimens obtained from four postmortem cases. We describe the four cases, to include pertinent autopsy findings and decedent histories, together with quantitative results for 5F-PB-22 determined in postmortem blood and antemortem serum. Samples were prepared via a liquid-liquid extraction at pH 10.2 into hexane : ethyl acetate. Instrumental analysis was achieved with liquid chromatography coupled with electrospray ionization tandem mass spectrometry operating in multiple reaction monitoring mode. Two ion transitions were monitored for the analyte of interest, and one ion transition was monitored for the internal standard. The observed concentration range of 5F-PB-22 is 1.1-1.5 ng/mL for three postmortem blood specimens and one antemortem serum specimen. Three of the decedents experienced abrupt, sudden death; however, one decedent expired after a rapidly deteriorating hospital course.

Fatal Intoxications with 25B-NBOMe and 25I-NBOMe in Indiana During 2014

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.

Case reports of synthetic cannabinoid XLR-11 associated fatalities.

Synthetic cannabinoids have been available in herbal incense and potpourri products over the Internet and in smoke shops for the last several years. We report the deaths of two individuals that were associated with XLR-11. Specimens were extracted via a liquid-liquid extraction at basic pH into hexane:ethyl acetate and analyzed by liquid chromatography tandem mass spectrometry. For these two case reports, we describe the instrumental analysis and extraction methods for XLR-11, toxicological results for postmortem blood specimens, relevant case information and autopsy findings. We also briefly review any previously published peer-reviewed reports in which XLR-11 was analytically confirmed and determined to be an intoxicating agent.

Identification of Novel Third-Generation Synthetic Cannabinoids in Products by Ultra-Performance Liquid Chromatography and Time-of-Flight Mass Spectrometry

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.

Death Associated With the Use of the Synthetic Cannabinoid ADB-FUBINACA

Synthetic cannabinoids have been found in herbal incense products for the last several years. We report the rapid death of an individual that was certified as synthetic cannabinoid-associated. The autopsy blood specimen was extracted by a liquid-liquid extraction at pH 10.2 into a hexane-ethyl acetate mixture and analyzed by a generalized synthetic cannabinoid LC-MS-MS method. For this case report, we briefly describe the instrumental analysis and extraction methods for the detection of ADB-FUBINACA in postmortem blood, toxicological results for the postmortem blood specimen (ADB-FUBINACA, 7.3 ng/mL; THC, 1.1 ng/mL; THC-COOH, 4.7 ng/mL), case information and circumstances and pertinent findings at autopsy. The cause of death was certified as coronary arterial thrombosis in combination with synthetic cannabinoid use. Manner of death was accident.

Death after use of the synthetic cannabinoid 5F-AMB.

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.

Detection of Carfentanil by LC–MS-MS and Reports of Associated Fatalities in the USA

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.

Three Cases of Fatal Acrylfentanyl Toxicity in the United States and a Review of Literature

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.

Synthetic Cannabinoid Product Surveillance by LC/ ToF in 2013-2015

Synthetic Cannabinoid Product Surveillance by LC/ ToF in 2013-2015 For the last several years, herbal incenses sold in smoke shops and on the Internet have been shown to contain various synthetic cannabinoids. As these compounds are subsequently controlled by either federal or state governments, new compounds are used and become prevalent. In 2013-2015, we detected new chemical structure subsets of cannabinoid compounds - the quinolinylindole carboxylates and the indazole carboxamides. Following a solvent extraction with acetonitrile:methanol, we used liquid chromatography-time of flight mass spectrometry (LC/ToF) to identify these compounds. Separation was performed via a gradient elution of acidified water and acetonitrile mobile phases on a C18 stationary phase held at 60°C. Time of flight mass spectrometry was performed in positive electrospray ionization mode. One low voltage scan was performed for precursor mass identification and one higher voltage scan was performed for product mass identification via insource collision induced dissociation. Newly detected compounds were the quinolinylindole carboxylates, PB-22 and 5F-PB-22, and the indazole carboxamides, AB-CHMINACA, AB-FUBINACA, ABPINACA, and ADB-FUBINACA. These compounds were detected as the sole adulterant in products as well as alongside other synthetic cannabinoids.

A Guide for the Interpretation of Postmortem Methamphetamine Findings: A Series of Case Reports

A Guide for the Interpretation of Postmortem Methamphetamine Findings: A Series of Case Reports Incidents involving illicit methamphetamine have demonstrated a dramatic increase in recent years. This prevalence has been attributed to its low cost, availability and extended duration of action. Furthermore, the ease of production from inexpensive, readily available materials has contributed to its increased production and distribution. When used moderately, effects include euphoria, increased heart rate, elevated blood pressure, reduced appetite and loss of inhibition. Excessive or chronic use may lead to manic and violent behavior, dizziness, confusion, hyperthermia, seizure, cardiorespiratory depression and death.