Alpha-methyltryptamine and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) fatal co-intoxication: case report and review of literature.

The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs ‒ alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) ‒ combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death.

Death by accidental intravenous administration of gasoline.

Herein, we present the case of accidental intravenous injection of gasoline in a 62-year-old male who was admitted to a dialysis center for his regular hemodialysis. Due to previous contact with another SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) positive patient, the hemodialysis was conducted in an isolated room. At the end of the procedure, the nurse, wearing all necessary personal protective equipment (PPE), in the intent to clean the dialysis catheter, applied medical gasoline, instead of 0.9% sodium chloride, intravenously to the patient. Soon afterwards, the patient's clinical condition deteriorated, and cardiopulmonary resuscitation was started. Despite the immediate reaction of the medical staff, after two successful cardiopulmonary reanimation and necessary intensive care measures, the patient suffered respiratory, metabolic, and lactic acidosis, hypotension, and tachyarrhythmia and ultimately died 7 h after the incident. The autopsy was conducted under the order of the district attorney. Main autopsy findings were marked congestion; right pleural and pericardial effusion; brain and lung edema; enlarged heart with left ventricle thickening and mild perivascular fibrosis; nephrosclerosis; tubular thyroidization; and interstitial fibrosis with inflammation. Gasoline presence was indisputably proven by conducted toxicology analysis in lung, bile, and brain samples. Traces of gasoline could be noted in the patient's blood sample in comparison to the blood that did not contain gasoline, but it was not possible to confidently claim that gasoline was present in the blood. Based on relevant findings, we concluded that the death of the patient was violent and that the cause of death was acute intoxication by gasoline.

Fatal intoxication with 1,4-butanediol: Case report and comprehensive review of the literature.

A fatal case of 1,4-butanediol (1,4-BD) oral ingestion is reported here, in which a 51-year-old man was found dead in his bed. According to the police report, the deceased was a known drug user. A glass bottle labeled (and later confirmed to be) "Butandiol 1,4" (1,4-BD) was found in the kitchen. Furthermore, the deceased's friend stated that he consumed 1,4-BD on a regular basis. The autopsy and histological examination of postmortem parenchymatous organ specimens did not revealed a clear cause of death. Chemical-toxicological investigations revealed gammahydroxybutyrat (GHB) in body fluids and tissues in the following quantities: femoral blood 390 mg/L, heart blood 420 mg/L, cerebrospinal fluid 420 mg/L, vitreous humor 640 mg/L, urine 1600 mg/L, and head hair 26.7 ng/mg. In addition, 1,4-BD was qualitatively detected in the head hair, urine, stomach contents, and the bottle. No other substances, including alcohol, were detected at pharmacologically relevant concentrations. 1,4-BD is known as precursor substance that is converted in vivo into GHB. In the synoptic assessment of toxicological findings, the police investigations and having excluded other causes of death, a lethal GHB-intoxication following ingestion of 1,4-BD, can be assumed in this case. Fatal intoxications with 1,4-BD have seldom been reported due to a very rapid conversion to GHB and, among other things, non-specific symptoms after ingestion. This case report aims to give an overview to the published of fatal 1,4-BD-intoxications and to discuss the problems associated with detection of 1,4-BD in (postmortem) specimens.

Ethylene glycol poisoning may be associated with elevated post-mortem vitreous glucose level.

Ethylene glycol (EG) is a toxic chemical that is sometimes used as ethanol substitute. Besides the desired intoxicating effects, the intake of EG may often lead to death unless timely treatment measures are provided by medical professionals. We examined 17 fatal EG poisonings between 2016 and March 2022 in Finland in terms of forensic toxicology and biochemistry results and demographic information. Most of the deceased were male and the median (range) age was 47 (20-77) years. Of the cases, 6 were suicides, 5 accidents and in 7 cases the intent remained undetermined. In all cases, vitreous humour (VH) glucose was above the limit of quantitation 0.35 mmol/L (mean: 5.2 mmol/L; range 0.52-19.5 mmol/L). Other markers of the glycaemic balance were within the normal range in all except one case. As EG is not routinely screened for in most laboratories but only analysed in cases where the intake of EG is suspected, some fatal EG poisonings may remain unrecognised in post-mortem (PM) investigations. Although various conditions may induce hyperglycaemia, it is worthwhile keeping in mind that elevated PM VH glucose levels that cannot be otherwise explained may suggest intake of ethanol substitutes.

A Metabolomics-Based Study on the Discriminative Classification Models and Toxicological Mechanism of Estazolam Fatal Intoxication.

Fatal intoxication with sedative-hypnotic drugs is increasing yearly. However, the plasma drug concentration data for fatal intoxication involving these substances are not systematic and even overlap with the intoxication group. Therefore, developing a more precise and trustworthy approach to determining the cause of death is necessary. This study analyzed mice plasma and brainstem samples using the liquid chromatography-high resolution tandem mass spectrometry (LC-HR MS/MS)-based metabolomics method to create discriminative classification models for estazolam fatal intoxication (EFI). The most perturbed metabolic pathway between the EFI and EIND (estazolam intoxication non-death) was examined, Both EIND and EFI groups were administered 500 mg of estazolam per 100 g of body weight. Mice that did not die beyond 8 hours were treated with cervical dislocation and were classified into the EIND groups; the lysine degradation pathway was verified by qPCR (Quantitative Polymerase Chain Reaction), metabolite quantitative and TEM (transmission electron microscopy) analysis. Non-targeted metabolomics analysis with EFI were the experimental group and four hypoxia-related non-drug-related deaths (NDRDs) were the control group. Mass spectrometry data were analyzed with Compound Discoverer (CD) 3.1 software and multivariate statistical analyses were performed using the online software MetaboAnalyst 5.0. After a series of analyses, the results showed the discriminative classification model in plasma was composed of three endogenous metabolites: phenylacetylglycine, creatine and indole-3-lactic acid, and in the brainstem was composed of palmitic acid, creatine, and indole-3-lactic acid. The specificity validation results showed that both classification models distinguished between the other four sedatives-hypnotics, with an area under ROC curve (AUC) of 0.991, and the classification models had an extremely high specificity. When comparing different doses of estazolam, the AUC value of each group was larger than 0.80, and the sensitivity was also high. Moreover, the stability results showed that the AUC value was equal to or very close to 1 in plasma samples stored at 4 °C for 0, 1, 5, 10 and 15 days; the predictive power of the classification model was stable within 15 days. The results of lysine degradation pathway validation revealed that the EFI group had the highest lysine and saccharopine concentrations (mean (ng/mg) = 1.089 and 1.2526, respectively) when compared to the EIND and control group, while the relative expression of SDH (saccharopine dehydrogenase) showed significantly lower in the EFI group (mean = 1.206). Both of these results were statistically significant. Furthermore, TEM analysis showed that the EFI group had the more severely damaged mitochondria. This work gives fresh insights into the toxicological processes of estazolam and a new method for identifying EFI-related causes of mortality.

"Spice"-related deaths in and around Munich, Germany: A retrospective look at the role of synthetic cannabinoid receptor agonists in our post-mortem cases over a seven-year period (2014-2020).

Synthetic cannabinoid receptor agonists (SCRAs, "Spice") are a diverse group of recreational drugs, with their structural and pharmacological variability still evolving. Forensic toxicologists often rely on previous reports to assess their role in intoxication cases. This work provides detailed information on the "Spice"-related fatalities around Munich, Germany, from 2014 to 2020. All cases underwent an autopsy. Pharmaceutical and illicit drugs were detected and quantified in post-mortem peripheral blood or liver by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on circumstantial evidence, only those cases for which a prior consumption was suspected underwent additional analyses for SCRAs and other new psychoactive substances in post-mortem blood, liver or antemortem specimens. Drug concentrations, pathological findings at autopsy and case histories were considered to assess and rank the SCRAs' involvement in each death. Concentration ranges for the individual substances in blood were defined and their distribution patterns over the investigated period were determined and correlated with their legal status and local police seizures. We identified 41 different SCRAs among 98 fatalities. 91.8% were male, at a median age of 36 years. SCRAs played a causative role in 51%, contributory role in 26%, and an insignificant role in 23% of cases. In correlation with local police seizures and legal status, 5F-ADB was the most prevalent in our cases, followed by 5F-MDMB-PICA and AB-CHMINACA. Cumyl-CBMICA and 5F-MDMB-P7AICA were among the least frequently detected SCRAs. "Spice"-related fatalities and SCRAs' causative role have significantly decreased among our cases since the German New Psychoactive Substances Act.

HPLC-MS/MS determination and the postmortem distribution or postmortem redistribution of paraquat and its metabolites in four fatal intoxication cases.

HPLC-MS/MS analysis and postmortem distribution or postmortem redistribution of paraquat and its two metabolites in poisoning death cases were reported. Paraquat, monoquat, and paraquat monopyridone were extracted from the sample with acetonitrile or methanol, respectively, detected by ZORBAX HILIC Plus (4.6 × 100 mm, 3.5 µm) chromatographic column, with 0.1 % formic acid aqueous solution - 0.1 % formic acid acetonitrile solution (v/v) as mobile phase. Paraquat, monoquat, and paraquat monopyridone had a good linear relationship within the range of 10-1000, 1-400, and 1-1000 ng/mL (or g), the correlation coefficient (r) were all ≥ 0.9996. Their detection limits were lower than 1 ng/mL (or g). The detection accuracy was 91.25∼113.44 %. The intra-day and inter-day precision were 1.51-3.99 % and 1.92-4.93 %, respectively. This method was used to detect and analyze four rare paraquat poisoning cases. The distribution of paraquat, monoquat, and paraquat monopyridone is uneven, which is relatively high in the heart, blood, lung, and kidney. Heart blood/Peripheral blood ratio of paraquat, monoquat, paraquat monopyridone concentration in two poisoned cases were 1.4, 2.0, 1.5 and 1.9, 1.3, 1.2, which showed a location dependent postmortem redistribution. This is the first time that HPLC-MS/MS and the postmortem distribution or postmortem redistribution of paraquat metabolites in poisoned death cases have been reported. This research provides scientific basis for forensic identification of paraquat poisoning cases and extraction of biological specimen.

Epiglottis Cartilage, Costal Cartilage, and Intervertebral Disc Cartilage as Alternative Materials in the Postmortem Diagnosis of Methanol Poisoning.

Alternative materials for postmortem diagnosis in the case of fatal poisonings are much needed when standard materials, such as blood and urine, are unavailable. The study presents a case of fatal mass methanol intoxication resulting from industrial alcohol consumption. The study aimed to determine methanol and formic acid concentrations in epiglottis cartilage, costal cartilage, and intervertebral disc cartilage and to analyze the correlation between their concentrations in cartilage tissues and the femoral blood. Methanol and formic acid concentrations in samples collected from 17 individuals (n = 17) were estimated using gas chromatography with flame ionization detection (GC-FID). Methanol concentration in the costal cartilage correlated with its concentration in the femoral blood (r = 0.871). Similar correlations were found for epiglottis cartilage (r = 0.822) and intervertebral disc cartilage (r = 0.892). Formic acid concentration in the blood correlated only with its concentration in urine (r = 0.784) and the epiglottis (r = 0.538). Cartilage tissue could serve as an alternative material for methanol analyses in postmortem studies. Formic acid, a methanol metabolite, does not meet the requirements for its presence determination in cartilage tissues.

Increased lung weight in fatal intoxications is not unique to opioid drugs.

Fatal intoxications with opioids are known to be associated with an increased lung weight, as well as with brain and pulmonary edema and urinary retention. However, there is evidence to suggest that fatal intoxications with non-opioid substances are also associated with increased lung weight; however, the latter aspect has not been comprehensively analyzed. To determine to what extent opioid and non-opioid substances are associated with increased lung and brain weight, we studied these organs in cases where the cause of death was attributed to intoxication with a single agent. Using data from cases autopsied at the National Board of Forensic Medicine (NBFM) in Sweden from 2009 through 2019 where the cause of death was attributed to a single substance, we created models of combined lung weight and brain weight. The models used age and sex as predictors as well as nested varying effects for the specific intoxicant and category of intoxicant. Suicidal hanging with negative toxicology cases served as controls. The population majority was male among both intoxications (68%) and controls (83%). The most common single substance group was opioids. All tested substances were associated with heavier lungs than controls, with the largest effect in the opioid group. Our findings show that several substances are associated with increased lung weight and that among intoxication deaths there is no difference in expected brain weight between substances. Hence, heavy lungs, without a reasonable explanation, should prompt a broad toxicological screening.

A fatal case involving the highest ever reported 4-CMC concentration.

Synthetic cathinones comprise a large amount of substances present on the dark market, which creates an undeniably worldwide problem and still is posing a threat. A 22-year-old man was brought to the Emergency Room from a party, where he had ingested orally 20 g of mephedrone. The man exhibited a disorder of consciousness with no logical verbal contact and dilated pupils. Moreover, a metabolic acidosis was present. The patient died after an hour from an admission to the ER. Blood and vitreous humor collected during an autopsy were analyzed with the use of an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-QqQ-MS/MS) with the use of C18 column in multiple reaction monitoring (MRM) mode. Both biological specimens were prepared using liquid-liquid extraction (LLE) with the use of ethyl acetate and 0.5 M ammonium carbonate water solution (pH 9). The limit of quantification (LOQ) of the method was 0.5 ng/ml in both matrices; precision and accuracy values did not exceed ±15%. Recovery of the method was in the range of 86.1%-102.7%. Determined concentrations of 4-CMC were 8542 and 9874 ng/ml in blood and vitreous humor, respectively. Other substances present in both biological materials were: atropine, diazepam, lidocaine, and its metabolite norlidocaine, as well as methcathinone and ethyl alcohol. The concentration presented in here described case is the highest ever reported 4-CMC concentration. Important aspect is also receiving other NPS by recreational users than intended, which lead to accidental poisoning (in presented case user assumed 4-CMC was 4-MMC).

Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice.

Diagnosing the cause of fatal intoxication by antipsychotic agents is an important task in forensic practice. In the 2020 Annual Report of the American Association of Poison Control Centers, among 40 deaths caused by antipsychotics, 21 cases were diagnosed as "probably responsible", thereby indicating that more objective diagnostic tools are needed. We used liquid chromatography-mass spectrometry-based integrated metabolomics analysis to measure changes in metabolic profiles in the plasma of mice that died from fatal intoxication due to chlorpromazine (CPZ) or olanzapine (OLA). These results were used to construct a stable discriminative classification model (DCM) comprising L-acetylcarnitine, succinic acid, and propionylcarnitine between fatal intoxication caused by CPZ/OLA and cervical dislocation (control). Performance evaluation of the classification model in mice that suffered fatal intoxication showed relative specificity for different pharmacodynamic drugs and relative sensitivity in different life states (normal, intoxication, fatal intoxication). A stable level of L-acetylcarnitine and variable levels of succinic acid and propionylcarnitine between fatal-intoxication and intoxication groups revealed procedural perturbations in metabolic pathways related to fatal intoxication by CPZ/OLA. Additional stability studies revealed that decomposition of succinic acid in fatal-intoxication samples (especially in the OLA group) could weaken the prediction performance of the binary-classification model; however, levels of these three potential metabolites measured within 6 days in fresh samples kept at 4 °C revealed a good performance of our model. Our findings suggest that metabolomics analysis can be used to explore metabolic alterations during fatal intoxication due to use of antipsychotic agents and provide evidence for the cause of death.

Toxicological Aspects of Methotrexate Intoxication: Concentrations in Postmortem Biological Samples and Autopsy Findings.

The aim of this study was the establishment of a UHPLC-QqQ-MS/MS method to determine methotrexate in postmortem biological samples and quantify the postmortem distribution of methotrexate in a case of fatal intoxication of this drug. A volume of 100 µL or 100 mg of postmortem specimens was precipitated with 400 µL of cold methanol and then analyzed using UHPLC-QqQ-MS/MS. The validation parameters of the method were as follows: limit of quantification: 0.1−1.0 ng/mL or ng/g, coefficient of determination: >0.998 (R2), matrix effect, intra- and inter-day accuracies and precisions: not greater than 13.6%, 14.8% and 17.4%, respectively. The recoveries were: 89.0−113.6%. The postmortem distribution studies revealed methotrexate concentrations as follows: blood­7.2 ng/mL, vitreous humor­0.8 ng/mL, liver­43.7 ng/g, kidney­20.6 ng/g, bone marrow­29.9 ng/g, lumbar vertebra­20.0 ng/g. The highest concentrations of methotrexate after poisoning were found in the tissues with the most rapidly dividing cells. The method described is simple, precise and selective. Methotrexate concentrations can be routinely determined in postmortem specimens. Determination of methotrexate in the postmortem biological material is possible after a few days of intensive treatment.

Intoxicación letal por opio por el consumo de ejemplares silvestres de Papaver somniferum / Fatal intoxication by opium from wild specimens of Papaver somniferum

Se reporta un caso de muerte por consumo de opio y se destaca la contribución de la toxicología forense en el esclarecimiento de la misma. La víctima fue un varón de 20 años quien tras recoger cápsulas de adormidera (Papaver somniferum L) pertenecientes a ejemplares que crecían de manera silvestre en un campo de la provincia de Toledo, y consumir el contenido de las mismas, falleció al día siguiente tras presentar dificultades respiratorias. La autopsia reveló pulmones edematosos, y las muestras de sangre y humor vítreo fueron remitidas al Servicio de Drogas del Instituto Nacional de Toxicología y Ciencias Forenses en Madrid, así como un fragmento de la sustancia vegetal que resultó resina de hachís. Alcaloides del opio (morfina, codeína, noscapina y tebaína), anfetaminas y cannabinoides fueron hallados en los análisis químico-toxicológicos. Se dictaminó que fue una muerte violenta de etiología accidental por policonsumo de drogas, con un rol preponderante del consumo de opio. (AU)

A new fatality due to opium consumption is reported here and the importance of Forensic Toxicology in clarifying this death is highlighted. The deceased was a 20-year-old male who, after collecting opium poppy capsules (Papaver somniferum L) which grew wild in a field near Toledo and consuming his latex (opium), died the next day after presenting respiratory difficulties. The Autopsy revealed congestive lungs and blood and vitreous humor samples were submitted to the Drugs service of the National Institute of Toxicology and Forensic Sciences in Madrid, as well as a piece of vegetal substance, which was identified as hashis. Cannabinoids, amphetamine and opium alkaloids (morphine, codeine, noscapine and tebaine) were found in the toxicologycal analysis. As conclusion, a violent death of accidental etiology due to mixed drug intoxication is here presented. In our opinion, the opium consumption had a preponderant toxic role in this fatality. (AU)

Natural cururu toad (Rhinella sp.) poisoning in a free-ranging lesser grison (Galictis cuja): Outcomes in a new susceptible predator with a novel peptide description.

Cururu toad (Rhinella marina group) is widely distributed in Brazil. Lesser grison (Galitic cuja) is a South American mustelid. This is the first report of natural poisoning in a free-ranging lesser grison by Rhinella toad parotoid gland secretion (PGS). Five minutes after biting a toad, the lesser grison developed convulsion, dying within 1.5 h. Mass spectrometry analysis of a milky-whitish secretion found in the lesser grison oral cavity allowed identification of a bufotoxin and a new bufonid peptide.

The dark side of social media: Two deaths related with chloroform intoxication.

A suicide pact is an agreement between people to commit suicide together, which usually takes place at the same time, in the same place, by using the same method. Social media serve as a way of communication between people. Thus, they use such platforms to find potential suicide pact partners. Chloroform, although being regarded to as a slightly forgotten poison, is still linked to homicide and suicide cases. Death due to an acute chloroform ingestion may be a result of central nervous system depression. In this paper, we present application of headspace gas chromatographic method using a dual column/dual flame ionization detector (HS-GC-FID/FID) for the determination of chloroform in two fatal intoxication cases, as well as chloroform stability study. Analysis of biological samples revealed chloroform concentrations of 135.8, 16.1, 8.1, and 37.1 µg/ml in blood, urine, vitreous humor, and bile, respectively. Kidney, liver, and muscle specimens contained 119.5, 99.6, and 28.4 µg/g of chloroform, respectively. The results of stability studies indicate the highest decrease of chloroform in room temperature, so it is advised to store samples in a freezer. The addition of sodium fluoride is recommended as in blood samples collected to the test tubes without any preservative agent, the detection of chloroform after 91 days is almost impossible. It is important to emphasize that even old poisons can cause a lot of concerns today, as here described cases are linked to chloroform intoxication, as well as with possible danger which social media bring about nowadays.

Determination of 3-MeO-PCP in human blood and urine in a fatal intoxication case, with a specific focus on metabolites identification.

3-Methoxyphencyclidine (3-MeO-PCP) is a new psychoactive substance that belongs to the phencyclidines family, first identified in Europe in 2012. This drug presents a stronger binding to N-methyl-D-aspartate (NMDA) receptors when compared to phencyclidine, which results in more potent effects, even at low concentrations. Very few articles have been published regarding 3-MeO-PCP in forensic toxicology. In this paper, the authors present a fatal 3-MeO-PCP intoxication case. In addition to the detection of the parent drug, metabolites were investigated in urine and, for the first time in the scientific literature, in blood. 3-MeO-PCP and its metabolites were quantitated by liquid chromatography-tandem mass spectrometry system (LC-MS/MS). Identification was confirmed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). 3-MeO-PCP tested positive in femoral blood (3 525 ng/mL) and urine (7 384 ng/mL). The femoral blood concentration was higher than the fatal concentrations range already reported in the literature (from 50 to 3 200 ng/mL). 3-MeO-PCP metabolites, including O-demethyl-3-MeO-PCP, piperidine-OH-3-MeO-PCP, O-demethyl-piperidine-di-OH-3-MeO-PCP and piperidine-di-OH-3-MeO-PCP, were detected in blood. In addition, two new metabolites, O-demethyl-piperidine-OH-3-MeO-PCP and O-demethyl-cyclohexyl-OH, were identified in both blood and urine. Unfortunately, due to the lack of reference material on the market, it was not possible to measure the concentration of these metabolites. However, the ratios between the metabolites and the parent drug were useful to estimate their analytical response and prevalence. At this time, considering the low ratios (<1) between metabolites and parent drug, metabolites testing does not seem useful to increase the detection window of the drug.

The utility of lung weight to heart weight ratio as a means to identify suspected drug intoxication deaths in a medico-legal autopsy population.

Fatal intoxications are common in a medico-legal autopsy setting and are associated with sparse findings during autopsy. It has been suggested that an increased lung weight may be associated with such fatalities. Previous literature is generally limited to a descriptive approach, including only opioid deaths, and lacking a definition of "heavy" lungs. Our aim was to create a model to identify cases with heavy lungs and to assess the predictive power of "heavy" lungs in identifying cases of different types of fatal intoxications during autopsy in an unselected medico-legal autopsy population. We identified all medico-legal autopsy cases ≥18 years in Sweden from 2000 through 2013. The lung weight to heart weight (LWHW) ratio was calculated. The positive predictive values (PPV) and negative predictive values (NPV) of both lung weight and LWHW ratio were calculated. Mean lung weight was higher in the intoxication group but the predictive power in the individual case was limited. Lung weight to heart weight ratio had better predictive power than lung weight alone, with a PPV of at most 0.15(0.14, 0.16 95% CI), while the NPV was 0.96 (0.95, 0.96 95% CI). The association between fatal intoxication and increased lung weight was positive, regardless of method and cutoffs used. While the PPV was poor, the NPV could reduce suspicion of fatal intoxication in the absence of other information. LHWH ratio is only a probability factor for fatal intoxication; accurate cause of death determination-as always-requires consideration of circumstances, autopsy, and toxicologic findings.

Old Poison, New Problem: Cyanide Fatal Intoxications Associated with Internet Shopping.

Widespread access to the Internet has an increasing influence on how suicides are committed. On websites such as eBay® or Amazon.com® highly toxic substances including cyanides are available for purchase. In the last 5 years, a few fatal intoxications associated with Internet shopping and buying "suicide kits" have been reported. Epidemiology of intoxications reported by American Association of Poison Control Centers between 2000-2018 shows that about 10% of all exposures to cyanide were related to suicide attempts and intentional ingestion of this substance. In order to determine the cyanide concentration in four fatal intoxication cases associated with Internet shopping, a headspace gas chromatography with dual column/dual flame ionization detector (HS-GC-FID/FID) method was validated and applied to casework. The method was linear in range, from 1 to 50 µg/mL, with a coefficient of determination of 0.999 (R2). The limit of quantification was 1.0 µg/mL; the detection limit was 0.5 µg/mL. Intra- and inter-day validation precision and accuracy did not exceed 10% and 15%, respectively. Recovery and matrix effect values ranged from 94.8- 103.8% and -5.2─3.8%, respectively. The cyanide concentrations were determined in biological fluids (blood, urine, bile, vitreous humor, gastric content) and postmortem tissue samples (spleen, kidney, liver, brain). The headspace gas chromatographic method, which is routinely used in clinical and forensic toxicology to quantify ethanol with its congeners (methanol, acetone, isopropanol, n-propanol and n-butanol), can be also applied to determine cyanide in intoxication cases. The global problem of a high number of suicides each year, requires increasing and more restrictive control of highly toxic substances available online as well as caution monitoring of human exposure to cyanide. This old and well known poison is being increasingly used nowadays for suicidal purposes, therefore determination of cyanide in biological samples is still important in terms of clinical and forensic toxicology.

Fatal intoxication involving 4-methylpentedrone (4-MPD) in a context of chemsex.

4-methylpentedrone (4-MPD) is a new psychoactive substance (NPS) belonging to the cathinone class. We report an original case of death mainly involving 4-MPD, along with cocaine, sildenafil, bromazepam and nevirapine. The investigation data and the autopsy findings indicated fatal intoxication in a chemsex context (drug use during sex). 4-MPD concentrations were determined in peripheral blood (1285 ng/mL), cardiac blood (1128 ng/mL), urine (>10,000 ng/mL), bile (1187 ng/mL) and vitreous humor (734 and 875 ng/mL in left and right samples, respectively) by gas chromatography (GC) coupled to tandem mass spectrometry. 4-MPD metabolites were explored by GC coupled to high resolution mass spectrometry. Due to the paucity of data concerning 4-MPD, its use and effects were gathered from online user testimonies. This case illustrates the toxicity of this infrequent pentedrone derivate and confirms the significant overdose risk associated with chemsex.

The adulterated XANAX pill: a fatal intoxication with etizolam and caffeine.

A 49-year old man was found dead at home next to a glass containing a dried, white, crystalline substance and near a bag containing pills with the imprint XANAX, the trade name of alprazolam. A comprehensive screening of material collected during the autopsy revealed the presence of etizolam and caffeine in lethal concentrations (0.77 µg/mL and 190 µg/mL) but no trace of alprazolam. Benzodiazepine analogue etizolam is rarely prescribed in Germany, and as a result there are not many reports about fatal cases. It has anxiolytic, hypnotic, sedative and muscle-relaxant properties and is used for the short-term treatment of anxiety and panic attacks. The purine alkaloid caffeine, conversely, is the most widely used central nervous system stimulant. The following report outlines potentially the first reported case of a lethal combination of the downer etizolam and the upper caffeine in medical literature.