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.

Circumstantial and toxicological features of deaths from self-administered intravenous anesthetic/narcotic agents.

For a better understanding of circumstantial and toxicological findings of fatalities resulting from self-administration of intravenous anesthetic/narcotic agents, medico-legal autopsy files of the State Institute of Legal and Social Medicine Berlin from 1998 to 2011 were reviewed retrospectively. Of a total of 15,300 autopsies, 9 cases of such deaths were identified, and all were health care professionals. Medical supplies for injection were found still on, or near, the body at the scene. Anesthetic/narcotic agents detected were classified into 3 categories, and administered solely or in combination. Propofol was the most common agent, being detected in 6 cases. In 2 out of 6 cases, propofol was detected substantially above therapeutic levels and was considered the cause of death. In the remaining 4 cases, propofol levels were within the therapeutic range, but propofol intoxication was considered as lethal due to it being administered by rapid continuous injection. In 5 cases, injection of opioid narcotics was fatal. Alongside the 2 propofol-detected cases, there was one case where a higher-than-therapeutic level of piritramide and a therapeutic level of alfentanil was identified. Despite suspected usage, remifentanil was not detected due to its rapid metabolism by elastases in one case, and sufentanil was undetectable due to putrefaction in another, but death was attributed to their potent respiratory depressant effects without respiratory assistance. Benzodiazepines were detected in 4 cases. All of them were used together with propofol or opioids, and contributed to death by inhibiting respiration. It is essential to consider means of administration as well as additive or synergistic effects of combined agents when interpreting toxicological results in such cases.

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.

Eight cases of fatal and non-fatal poisoning with Taxus baccata.

This paper describes two fatalities, three non-fatal intentional and three accidental oral ingestions of yew (Taxus baccata) leaves. In all cases the post-mortem external examinations showed no signs of violence. Internal examinations revealed small green, needle-like particles on the tongue, in the esophagus and in the stomach. Yew leaves were also identified in the stomach contents, whereas Taxus leaves were cut into small pieces and then ingested in one case. The analytical method used was based on a liquid-liquid-extraction under alkaline conditions followed by LC-MS/MS analysis (QTRAP 5500). Chromatographic separation was achieved by HPLC on a Kinetex C18 2.6u (100×3) mm. The analytical method allows the simultaneous identification and quantification of the commercially available yew alkaloids taxoids (m/z): paclitaxel (854.2→105.0/286.1), 10-deacetyltaxol (10-DAT: 812.2→105.0/286.1), baccatin III (BAC III: 604.0→105.0/327.0), 10-deacetylbaccatin III (10-DAB III: 562.1→105.0/327.0), cephalomannine [taxol B] (562.1→105.0/327.0) and of 3,5-dimethoxyphenol (3,5-DMP: 155.0→111.9/122.9) also encompassing the qualitative analysis of the alkaloidal diterpenoids (Q1→194.0/107.0); reference mass spectra obtained from a yew leaves extract: monoacetyltaxine (MAT: 568.4), taxine B (584.2), monohydroxydiacetyltaxine (MHDAT: 626.4), triacetyltaxine (TAT: 652.4), monohydroxytriacetyltaxine (MHTAT: 668.4). In both fatalities, paclitaxel, 10-DAT and cephalomannine were not identified in urine, cardiac and femoral blood but all taxoids and 3,5-DMP were present in stomach content and excreted into the bile. In urine, highest 3,5-DMP concentration was 7500 µg/L and 23,000 µg/L after enzymatic hydrolysis, respectively. In intentional and accidental poisonings, when electrocardiogram (ECG) examinations revealed ventricular tachycardia and/or prolonged QRS intervals, taxines were identified in plasma/serum, even after the ingestion of a few number of yew leaves, when 3,5-dimethoxyphenol was not even found. According to the data from one near-fatal intentional poisoning, elimination half-life of MAT, TAXIN B, MHDAT and MHTAT in serum was calculated with 11-13 h and taxines were detected up to t=+122 h post-ingestion of approximately two handfuls of yew leaves.