Forensic Toxicology最新文献

Background/purpose: Mephedrone, a ring-substituted synthetic cathinone derivative, gained popularity as a recreational drug in the late 2000s. Reports of fatalities related to mephedrone use have emerged with varying concentrations of blood mephedrone upon forensic investigations. This study aims to evaluate the existing literature on mephedrone concentrations in instances of clinical intoxication and fatal cases.

Methods: We comprehensively searched electronic databases, including Web of Science, PubMed, Embase, and the Cochrane Library, from inception to July 26, 2023. We selected case reports or case series of mephedrone intoxication presented with individual blood mephedrone concentration. Patient demographics, clinical characteristics, blood mephedrone concentrations, and outcomes were extracted for analysis.

Results: 77 cases from 14 case reports and 6 case series were identified for review. There were 34 deaths and 43 non-fatal intoxication cases. The median patient's age was 24 years (IQR: 10), and 91.4% were male. Forty-five of the 63 cases (71.4%) were reported with alcohol or other illicit drugs detected. The median blood mephedrone concentration was 0.37 mg/L (IQR: 1.09 mg/L). Death cases were older than non-fatal cases (median = 30 vs. 22 years, p = 0.029). The median blood mephedrone concentration was higher in death cases (1.30 mg/L vs. 0.12 mg/L, p < 0.0001).

Conclusions: Blood mephedrone concentration in dead patients is approximately 11 times higher than in non-fatal cases. This finding could serve as a stepping stone to the diagnosis of concentrations in clinical poisoning cases and deaths, especially in the treatment of poisoning patients. In more extensive prospective studies, further research is necessary to establish a standardized, real-time available methodology and validate the predictive value of mephedrone concentrations in the prognostic value of mephedrone concentrations.

Purpose: The most commonly associated substance found in Ecstasy tablets is MDMA (3,4-methylenedioxymethamphetamine). In our study, we showed how the composition of psychoactive ingredients in Ecstasy tablets seized on the drug market in Poland has changed in the years 2005-2020.

Methods: The study material consisted of nearly 20,000 single Ecstasy tablets seized by representatives of law enforcement (the police, prosecutors) from 2005 to 2020 and analysed by the Institute of Forensic Research, Krakow, Poland. The analysis of the tablets was carried out by gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography with diode array detection (HPLC-DAD) and ultra-high-performance liquid chromatography with photodiode array detection (UHPLC-PDA).

Results: Currently, new types of MDMA tablets are introduced onto the market, available in various colours and shapes. Our study showed that tablets sold on the street as Ecstasy have variable purity and sometimes contain little or no MDMA. The mean content of MDMA in one tablet seized in 2005-2011 decreased from 90 to 50 mg. In 2013, Ecstasy tablets with a very high MDMA content (average 195 mg per tablet) appeared on the market, but in the next 2 years, the MDMA content decreased again. From 2016, the average MDMA content began to rise again, ranging from 60 to 280 mg.

Conclusion: Tablets sold as Ecstasy also contained completely different psychoactive substances, including new psychoactive substances (NPS) (found in almost 20% of all examined tablets sold as Ecstasy) belonging to different chemical groups or their dangerous combinations (i.e. phenylethylamines, piperazines, tryptamines, cathinones, arylalkylamines, arylcyclohexylamines and piperidines). Such a large variety of psychoactive substances in Ecstasy tablets is associated with a high risk for users unaware of their composition.

Purpose: Toxicological analyses of biological samples play important roles in forensic and clinical investigations. Ingested drugs are excreted in urine as conjugates with endogenous substances such as glucuronic acid; hydrolyzing these conjugates improves the determination of target drugs by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, we sought to improve the enzymatic hydrolysis of glucuronide conjugates of five psychoactive drugs (11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol, oxazepam, lorazepam, temazepam, and amitriptyline).

Methods: The efficiency of enzymatic hydrolysis of glucuronide conjugates in urine was optimized by varying temperature, enzyme volume, and reaction time. The hydrolysis was performed directly on extraction columns. This analysis method using LC-MS/MS was applied to forensic autopsy samples after thorough validation.

Results: We found that the recombinant β-glucuronidase B-One® quantitatively hydrolyzed these conjugates within 3 min at room temperature directly on extraction columns. This on-column method saved time and eliminated the loss of valuable samples during transfer to the extraction column. LC-MS/MS-based calibration curves processed with this method showed good linearity, with r² values exceeding 0.998. The intra- and inter-day accuracies and precisions of the method were 93.0-109.7% and 0.8-8.8%, respectively. The recovery efficiencies were in the range of 56.1-104.5%. Matrix effects were between 78.9 and 126.9%.

Conclusions: We have established an LC-MS/MS method for five psychoactive drugs in urine after enzymatic hydrolysis of glucuronide conjugates directly on extraction columns. The method was successfully applied to forensic autopsy samples. The established method will have broad applications, including forensic and clinical toxicological investigations.

Purpose: The aim of this study is to examine the clinical and imaging manifestations of methanol toxicity during the COVID-19 pandemic, as well as to review existing studies on this topic. The most common cause of methanol intoxication is methanol-adulterated liquor. The primary metabolite of methanol, formic acid, is responsible for pathological changes. Symptoms typically present within 6-24 h of consumption and can include visual disturbances, acute neurological symptoms, and gastrointestinal issues. During the initial year of the COVID-19 pandemic, methanol poisoning cases increased significantly.

Methods: In this study, We present six different patients with methanol intoxication and their clinical and imaging features.

Results: In the literature review, the most common clinical presentation was loss of consciousness and obtundation and the other was vision loss. CT scan findings showed bilateral putaminal necrosis and hemorrhage in 55% of methanol toxicity patients.

Conclusion: Methanol intoxication, causing bilateral putaminal involvement and a 50% mortality rate in intracerebral hemorrhage patients, warrants urgent toxicological analysis due to potential putaminal hemorrhage.

Purpose: NPB-22 (quinolin-8-yl 1-pentyl-1H-indazole-3-carboxylate), Adamantyl-THPINACA (N-(1-adamantantyl)-1-[(tetrahydro-2H-pyran-4-yl)methyl]-1H-indazole-3-carboxamide), and CUMYL-4CN-B7AICA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H- pyrrolo[2,3-b]pyridine-3-carboxamide), synthetic cannabinoids were evaluated in terms of CB₁ (cannabinoid receptor type 1) and CB₂ (cannabinoid receptor type 2) activities, and their biological effects when inhaled similar to cigarettes were examined.

Methods: The half maximal effective concentration values of the aforementioned synthetic cannabinoids at the CB₁ and CB₂ were investigated using [³⁵S]guanosine-5'-O-(3-thio)-triphosphate binding assays. In addition, their biological effects were evaluated using the inhalation exposure test with mice. The smoke generated was recovered by organic solvents in the midget impingers, and the thermal degradation compounds of the smoke components were identified and quantified using a liquid chromatography-photo diode array detector.

Results: NPB-22 and Adamantyl-THPINACA had equivalent CB₁ activity in in vitro assays. Meanwhile, NPB-22 had a weaker biological effect on some items on the inhalation exposure test than Adamantyl-THPINACA. When analyzing organic solvents in the midget impingers, it was revealed that NPB-22 was degraded to 8-quinolinol and pentyl indazole 3-carboxylic acid by combustion. In addition, these degradation compounds did not have CB₁ activity.

Conclusion: It was estimated that the biological effects of NPB-22 on the inhalation exposure test weakened because it underwent thermal degradation by combustion, and the resultant degradation compounds did not have any CB₁ activity in vitro.

Purpose: Riot Control Agents (RCAs) are chemicals used in law enforcement for non-lethal riot control and use in conflicts between states that violates the Chemical Weapons Convention. OPCW's Scientific Advisory Board has identified sixteen potential RCAs including capsaicinoids, CS, and CR. RCAs may be misused for criminal purposes, so methods for detecting such misuse are needed. This study therefore evaluates the feasibility of a rapid, high throughput screening method of RCAs on surfaces (particularly clothing surfaces) by Direct Analysis in Real Time with a thermal desorption unit coupled to high-resolution mass spectrometry (DART-TD-HRMS).

Methods: A broadly applicable method for detecting potential RCAs was developed and tested on cotton fabric samples sprayed with self-defence sprays from an in-house reference stock. The feasibility of detecting RCAs by direct analysis of surface wipe samples placed in the DART source was also investigated.

Results: The method detected all sixteen RCAs and contaminated clothing were successfully screened for active agents in a reference collection of self-defence sprays. A pilot study also showed that RCAs can be detected by holding a sample directly in front of the DART source.

Conclusion: DART-TD-HRMS enables rapid and simple screening of RCAs on fabric samples enabling a high sample throughput.

Purpose: The presence of cereulide, an emetic toxin produced by Bacillus cereus, in fried rice samples is critical evidence of food poisoning even in situations where B. cereus could not be detected. This study aims to develop a screening method for analyzing cereulide in fried rice using the QuEChERS procedure and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Methods: Cereulide was identified and quantified in fried rice samples using the QuEChERS extraction method and LC-MS/MS. The accuracies of the methods were determined by analyzing fortified blank samples at two concentrations (10 and 50 µg/kg) conducted on three samples daily for five days.

Results: The QuEChERS procedure removed matrix compounds from fried rice. Characteristic MS/MS spectra enabled the identification of cereulide. As the matrix effects in seven fried rice samples were within ± 6%, an external solvent calibration curve could be used for quantification. This method exhibited good accuracy ranging from 88 to 89%. The relative standard deviations for both repeatability and intra-laboratory reproducibility were < 4%. These standard deviations satisfied the criteria of the Japanese validation guidelines for residues (MHLW 2010, Director Notice, Syoku-An No. 1224-1). The limit of quantification was 2 μg/kg. The applicability of this method was confirmed using the analysis of cereulide in fried rice samples incubated with emetic Bacillus cereus.

Conclusions: The QuEChERS extraction procedure described herein showed substantial promise as a reliable screening tool for cereulide in fried rice sample.

Purpose: Synthetic cathinones constitute the second largest group of new psychoactive substances, which are often used for recreational purposes and reported in toxicological analysis. Various factors may influence the stability of synthetic cathinones between sampling and analysis, and therefore, stability studies are required to determine the best storage conditions as well as extend the period of detection.

Methods: This study involved sixteen synthetic cathinones and ten dihydro-metabolites spiked in human urine to evaluate the stability under common storage conditions to imitate real forensic toxicology samples. The samples were stored at either room temperature (22-23 °C) for up to 3 days, refrigerated (4 °C) for up to 14 days or frozen (-40 °C) for up to 12 months, and analyzed in triplicate using a validated liquid chromatography-tandem mass spectrometry method.

Results: Analytes' concentrations decreased over time, although slower when stored frozen. All analytes remained stable (> 80%) for 1 month when stored frozen before losses in content were more apparent for some compounds, depending on their chemical structure. Under all storage conditions, the highest instability was observed for analytes containing halogens (i.e., chlorine or fluorine). Thus, halogenated analytes were further investigated by using liquid chromatography coupled to quadruple time-of-flight mass spectrometry to attempt identifying degradation products.

Conclusions: Irrespective of parent analytes, dihydro-metabolites had improved stability at each tested temperature, which highlights their importance as appropriate urine biomarkers when retesting is required after a long period of storage.

Purpose: We have investigated the absorption dynamics of petroleum fuel components from the analytical results of autopsy samples.

Methods: Post-mortem samples of the severely burned case, including femoral blood, intratracheal contents (mucus) and intratracheal gas-phase samples were collected, and analysed by gas chromatography-mass spectrometer with head-space solid-phase microextraction.

Results: The composition of flammable substances in the tracheal gas phase differed slightly from that in mucus.

Conclusion: High-boiling point components are retained in the trachea, whereas relatively lower-boiling point components are detected predominantly in the tracheal gas phase and blood.

Purpose: Inadvertent and/or unknowing exposure to drugs and drug residues has been frequently debated in situations of so-called adverse analytical finding (AAF) in the context of sports drug testing programs. Transfer of drug residues via unprotected intercourse is a conceivable scenario but scientific data and authentic case reports are scarce. Herein, investigations into two AAFs with the peroxisome proliferator-activated receptor delta (PPARδ) agonist GW1516 are reported and discussed.

Methods: To probe for a contamination scenario involving sexual intercourse, two assays were used to determine semenogelin in human urine, with one employing an immunochromatographic lateral flow approach and another based on liquid chromatography-tandem mass spectrometry. Further, drug-residue testing using patients' ejaculate was conducted by utilizing liquid chromatography in conjunction with a triple quadrupole mass spectrometer, followed by re-analysis of suspect samples (i.e., samples indicating the presence of relevant compounds) using high resolution/high mass accuracy mass spectrometry.

Results: In one case, but not the other, the possibility of intimate contact as the source of the AAF was confirmed after a thorough investigation of potential contamination scenarios. Subsequent research revealed analytical evidence for the presence of seminal fluid in one of the female athlete's doping control urine samples, and the analysis of clinical ejaculate specimens provided first data on an authentic concentration level of GW1516 and its metabolites in human seminal fluid.

Conclusions: The combined facts substantiate the possibility of an AAF caused by unprotected sexual intercourse and the plausibility of the case-related arguments.