A Fatal Case Report Resulting from the Abuse of the Designer Benzodiazepines Clonazolam and Flualprazolam in Conjunction with Dried Opium Poppy Pods‡.

Toxicologists are often confronted with the abuse of multiple drugs and are obliged to decide which compound may have been the cause of death. We report on a 21-year-old man (182 cm, 84 kg), who was found unconscious in his bed. Beside him, the police found several controlled substances, among them were dried opium poppy pods containing thebaine, codeine and morphine, a clear liquid with the designer benzodiazepines flualprazolam and clonazolam and a white powder with the imprint SGT-25, instead of SGT-78 (CUMYL-4CN-BINACA). These compounds were also found in the urine sample following a non-targeted gas chromatography-mass spectrometry and a targeted liquid chromatography-tandem mass spectrometry (LC-MS-MS) screening approach. Subsequently, these compounds were quantified in whole femoral blood and scalp hair. Based on the concentrations measured in femoral blood in particular, we assume that the deceased had taken a lethal dose of the designer benzodiazepines-flualprazolam (0.74 mg/L) and clonazolam (2.08 mg/L), an extremely high dose of the opiates-thebaine (0.81 mg/L), codeine (0.23 mg/L) and morphine (0.13 mg/L ) and a high dose of the synthetic cannabinoid-CUMYL-4CN-BINACA (0.01 mg/L). Besides postmortem concentrations, we also present electron impact and electrospray ionization mass spectra of compounds found in the vicinity of the decedent, namely the tryptamines-4-hydroxy-N-isopropyl-N-methyltryptamine (4-HO-MIPT), 4-hydroxy-N-ethyl-N-methyltryptamine (4-HO-MET) and 4-acetoxy-N,N-diethyltryptamine (4-ACO-DET), the amphetamines-3-fluoroethamphetamine (3-FEA) and 2-fluoromethamphetamine (2-FMA) and the arylcyclohexylamines-N-ethyldeschloroketamine (O-PCE), 3-methoxyphencyclidine (3-MeO-PCP) and 3-methoxyeticyclidine (3-MeO-PCE).

Toxicological investigations in a death involving 2-MAPB.

New psychoactive substances are becoming increasingly popular. However, there is a lack of mass spectral information on parent substances and their corresponding metabolites as well as fatal concentrations in body liquids and tissues. Only very few clinical reports and user reports exist. This is also the case for methylaminopropylbenzofuran (MAPB) isomers. Urine from a decedent was screened using different immuno assays, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-high resolution mass spectrometry (LC-HRMS/MS). Additionally, respective targets were quantitated in all analyzed specimens by LC-MS/MS. Gas chromatography-infrared spectroscopy (GC-IR) was applied to confirm the identity of the intoxication. GC-MS and the amphetamine immuno assay were useful to track the putative intoxication. However, the chemical structure of 2-MAPB was only elucidated by means of LC-HRMS/MS and GC-IR. 2-MAPB was highest in urine (167 µg/mL), followed by gastric content (98.9 µg/mL), bile fluid (30.8 µg/mL), liver (22.2 µg/g), heart blood (16.7 µg/mL), and lowest in femoral blood (7.3 µg/mL). Besides the parent substance, we detected N-demethyl-2-MAPB and hydroxy-2-MAPB in the urine sample. This case report presents an intoxication caused by 2-MAPB. The 2-MAPB concentration found in femoral blood exceeded those reviewed for 5/6-MAPB. The concentrations of the other specimens cannot be evaluated because there exist no comparative data. The values presented can be applied to assess 2-MAPB intoxications in the future.

A Fatal Case Involving N-Ethyldeschloroketamine (2-Oxo-PCE) and Venlafaxine.

Methoxetamine, 3-methoxyphencyclidine or 3-methoxyeticyclidine are arylcyclohexylamines which have been abused in the past. However, the market for new psychoactive substances, in particular for research chemicals, is rapidly growing and new compounds are being regularly explored by users. Abuse can lead to clinical case and in the worst-case scenario to fatalities. We present the fatal case of a 52-year-old man, who was found dead in the bedroom by his fiancé. He had abused N-ethyldeschloroketamine and venlafaxine prior to his death. These compounds were retrieved from a non-targeted gas chromatography/mass spectrometry-based screening approach of a purified urine sample. In addition, deschloroketamine, bisoprolol and ramiprilate were found in the urine sample, but were either absent or only present at low level in femoral blood. During autopsy a number of tablets were found in the duodenum and identified as venlafaxine. Furthermore, N-ethyldeschloroketamine was quantified in various specimens taken during autopsy and the highest concentration was observed in liver (6,137 ng/g) followed by urine (3,468 µg/L), bile fluid (3,290 µg/L), gastric contents (3,086 µg/L), heart blood (2,159 µg/L) and liquor (1,564 µg/L). The smallest amount was found in femoral blood (375 µg/L). N-ethyldeschloroketamine was also found in the disposable syringes, in a beaker and on the spatula along with deschloroketamine, morphine, metamizole, oxycodone, flupirtin or ibuprofen. The concentrations presented-in particular for femoral blood-are a good starting point for evaluating N-ethyldeschloroketamine intoxications in the future. The other values are helpful for evaluating the post-mortem concentration distribution of this research chemical.

Another fatal case related to the recreational abuse of U-47700.

The abuse of synthetic opioids has become a major threat in recent years. Several clinical reports and fatal case reports exist discussing life-threatening hypoventilation and fatal respiratory depression following the abuse of trans-3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide (U-47700). The reported concentration of U-47700 in peripheral blood varies between 0.01 µg/mL and 1.46 µg/mL. These values depend on the mode of administration and whether the drug was used in combination with other drugs and/or pharmaceuticals. In the past, U-47700 was predominantly insufflated and not injected. The current study presents a non-targeted liquid chromatography/mass spectrometry (LC/MS)-based screening approach of urine and cerebrospinal fluid samples after intravenous injection of U-47700. Furthermore, quantitative values on U-47700 as obtained by liquid chromatography coupled to a linear ion trap (LC/ESI-QTRAPMS) are presented concerning femoral blood (0.29 µg/mL), urine (0.24 µg/mL), gastric contents (0.57 µg/mL), bile fluid (2.3 µg/mL), heart blood (1.25 µg/mL), liver (9.9 µg/g), cerebrospinal fluid (0.4 µg/mL), and hair (0.14 ng/mg). Thereof, concentrations in hair, gastric contents, bile fluid and cerebrospinal fluid have never been reported before. Drug paraphernalia were also analyzed by liquid chromatography coupled to a diode array detector (LC/DAD) and nuclear magnetic resonance spectrometer (NMR). The analyses show that the powder had a relatively high purity and was adulterated to a low degree. This is the first case report which lists concentration distributions of various specimens after intravenous injection. These findings as well as the U-47700 concentration are important to evaluate autopsy cases of U-47700 intoxication in the future.