Forensic Toxicology最新文献

Purpose: Fire victims often inhale hydrogen cyanide (HCN) gas in addition to carbon monoxide. This study aimed to investigate the current prevalence of HCN inhalation among fire victims and assess the contribution of HCN as a toxic factor in fire-related deaths.

Methods: The study included 29 cases of fire-related deaths, where autopsies were conducted at the Department of Legal Medicine, Osaka University, from April 2014 to March 2020. No resuscitation was performed before death was confirmed and blood samples were obtained from both the left and right cardiac chambers. Blood cyanide concentrations were measured. Additionally, a physiologically based pharmacokinetic model, as described by Stamyr et al. (Arch Toxicol 89:1287-1296, 2015), was used to simulate the time course of blood concentration changes for different inhaled HCN concentrations. The inhaled HCN concentration and inhalation time that minimized the difference between the measured and simulated blood concentrations were calculated.

Results: Cyanide was detected in the cardiac blood of 76.3% of cases. In all instances, left cardiac blood concentrations were higher than those in the right cardiac blood. The simulations using the physiologically based pharmacokinetic model revealed eight cases where the inhaled HCN concentration exceeded 5000 ppm, with an inhalation time of less than 0.5 min.

Conclusions: Many fire victims inhaled HCN gas, and in a few cases, it appears that death occurred rapidly after inhalation of high HCN concentrations. These findings suggest that the contribution of cyanide gas to fire-related deaths warrants closer examination.

Purpose: Identification and quantification of sulfide ion in biological samples are required in forensic purpose. Gas chromatography-mass spectrometry (GC/MS) has been used for the analysis of sulfide ion by using derivatization reagents. However, conventional derivatization reagents require special attention for derivatization. To simplify the derivatization protocol, we examined ethenesulfonyl fluoride (ESF) as a derivatizing reagent of sulfide ion.

Methods: To 100 μL of whole blood sample containing sulfide ion, 100 μL of boric acid buffer (pH 8.0), 100 μL of acetone solution containing internal standard, 100 μL of acetone solution containing 600 mM concentration of ESF, and 100 μL of hexane were added in a 1.5-mL plastic tube. The mixture was vortexed at room temperature, the tubes were centrifuged, and the organic layer was injected into the GC/MS.

Results: ESF exhibited higher reactivity toward sulfide ion than interfering compounds present in whole blood, allowing for selective derivatization. With the optimized protocol, the detection limit for sulfide ion was 0.01 μg/mL. The calibration curve showed good linearity (R² = 0.9999) in the range of 0.05-10.0 μg/mL, and the precision (% relative standard deviation) and the accuracy (% bias) were within ± 10% (intra- and inter-day).

Conclusion: This GC/MS-based method is a valuable tool for forensic investigations and various analytical fields, offering reliable quantification of sulfide ion in whole blood.

Purpose: The analysis of drug residues on some currencies is well-established in the literature. However, there is no published study describing the presence of drug residues on Turkish paper currency.

Methods: This study focused on the analysis of 14 drug residues present on 600 Turkish banknotes collected from three different cities: Ankara, Adana, and Istanbul. The banknotes underwent preparation by a non-destructive and straightforward extraction method using methanol. To investigate the extent of contamination a method was subsequently developed and validated for liquid chromatography triple quadrupole mass spectrometry analysis to detect and quantify the target analytes. The investigated substances included benzoylecgonine, cocaine, heroin, codeine, morphine, 6-monoacetylmorphine (6-AM), amphetamine, methamphetamine, 3,4-methylenedioxy-N-methamphetamine (MDMA), methyl 3,3-dimethyl-2-(1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido)butanoate (MDMB-4EN-PINACA), N-[1-(aminocarbonyl)-2,2-dimethylpropyl]-1-butyl-1H-indazole-3-carboxamide (ADB-BUTINACA), tetrahydrocannabinol (THC), pregabalin, ketamine, and tramadol.

Results: The calculated mean concentrations per note were 475.5 ng cocaine, 660.7 ng methamphetamine, 220.4 ng benzoylecgonine, 36.5 ng ketamine, 46.0 ng amphetamine, 120.6 ng 6-AM, 22.9 ng morphine, 6.3 ng codeine, 107.4 ng THC, 1.3 ng MDMB-4en-PINACA, 1.1 ng ADB-BUTINACA and 65.9 ng MDMA. Our findings indicate that banknotes commonly circulated in the three cities were primarily contaminated with methamphetamine and cocaine.

Conclusions: This study highlights the prevalence of drug residues on banknotes and raises concerns about their potential impact. The contamination of Turkish currency with drug residues is a strong indication of the widespread use of banknotes in drug trafficking.

Purpose: This study examined the applicability of hair analysis as an approach to identify suvorexant (SUV) and lemborexant (LEM) intake by analyzing black hair specimens collected from study participants after a single oral administration.

Methods: Hair specimens were collected form participants who took a single dose of 10 mg SUV or 5 mg LEM. Identification of the dual orexin receptor antagonists (DORAs) and their metabolites was performed by liquid chromatography-tandem mass spectrometry. Reference standards of S-M9 and L-M4, the metabolites of SUV and LEM, respectively, were synthesized in our laboratory. Sectional analysis of 1-mm segments of the single-hair strands was also performed to investigate the incorporation behavior of the drugs into hair.

Results: Unchanged SUV and LEM, and their metabolites S-M9 and L-M4 were detected even in the single-hair specimens. Results of the segmental hair analysis showed predominant incorporation of the drugs into hair through the hair bulb region rather than through the upper dermis zone of the hair root. The drug concentrations in the hair specimens, collected about 1 month after intake, were 0.033-0.037 pg/hair strand (0.17-0.19 pg/mg) for SUV and 0.054-0.28 pg/hair strand (0.28-1.5 pg/mg) for LEM. The calculated distribution ratios of the DORAs into hair to the oral doses were much lower than those of benzodiazepines and zolpidem reported in a previous study.

Conclusions: This is the first report of the detection of the DORAs in hair. The incorporation behavior of the DORAs into hair revealed herein are crucial for proper interpretation of hair test results.

Purpose: Pyrrolidinophenone derivatives (PPs) are amphetamine-like designer drugs containing a pyrrolidine ring, and their adverse effects resemble those of methamphetamine (METH). Microglial activation has been recently suggested as a key event in eliciting the adverse effects against dysfunction of the central nervous system. The aim of this study is to clarify the mechanisms of microglial activation induced by PPs.

Methods: We employed the human microglial cell line HMC3 to assess microglial activation induced by PPs and evaluated the capacities for proliferation and interleukin-6 (IL-6) production that are characteristic features of the activation events.

Results: The WST-1 assay indicated that viability of HMC3 cells was increased by treatment with sublethal concentrations (5-20 µM) of α-pyrrolidinooctanophenone (α-POP), a highly lipophilic PP, whereas it was decreased by treatment with concentrations above 40 µM. Treatment with sublethal α-POP concentrations up-regulated the expression and secretion of IL-6. Additionally, α-POP-induced increase in cell viability was restored by pretreating with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, and stattic, an inhibitor of signal transducer and activator of transcription 3 (STAT3), respectively, suggesting that activation of the ROS/STAT3 pathway is involved in the α-POP-induced activation of HMC3 cells. The increases in cell viability were also observed in HMC3 cells treated with other α-POP derivatives and METH.

Conclusions: These results suggest that enhanced productions of ROS and IL-6 are also involved in microglial activation by drug treatment and that HMC3 cell-based system is available to evaluate accurately the microglial activation induced by abused drugs.

Purpose: Food forensics is an emerging field and the initial part of this review showcases the toxic effects and the instrumental methods applied for the detection of the most commonly used azo dyes. Electrochemical detection has a lot of advantages and hence the significance of the most important techniques used in the electrochemical detection is discussed. The major part of this review highlights the surface modified electrodes, utilized for the detection of the most important azo dyes to achieve low detection limit (LOD).

Methods: A thorough literature study was conducted using scopus, science direct and other scientific databases using specific keywords such as toxic azo dyes, electrochemical detection, modified electrodes, LOD etc. The recent references in this field have been included.

Results: From the published literature, it is observed that with the growing interests in the field of electrochemical techniques, a lot of importance have been given in the area of modifying the working electrodes. The results unambiguously show that the modified electrodes outperform bare electrodes and offer a lower LOD value.

Conclusion: According to the literature reports it can be concluded that, compared to other detection methods, electrochemical techniques are much dependable and reproducible. The fabrication of the electrode material with the appropriate modifications is the main factor that influences the sensitivity. Electrochemical sensors can be designed to be more sensitive, more reliable, and less expensive. These sensors can be effectively used by toxicologists to detect trace amounts of harmful dyes in food samples.

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: We previously developed evaluation methods using micro-segmental analysis (MSA) to examine the effects of external environments on drug content in hair and nails. In this study, the effects of the natural environmental factors (water, temperature, humidity, light, and soil) on drug contents in nails were examined and compared with our previous experimental data on hair.

Methods: Four hay-fever medicines were used as model drugs (fexofenadine, epinastine, cetirizine, and desloratadine) to evaluate drug stability in the nails. Reference nails containing the four medicines were collected from patients with hay fever who ingested the medicines daily for four months. The nails were exposed to various natural environments for up to four months.

Results: The effects of temperature, humidity, and light on drug contents in the nails were comparatively small. Soil significantly decomposed the nail surfaces and decreased the drug content of the nails (up to 17 %). Water also decreased the drug content (up to 12 %), although no apparent changes in nail surfaces were observed.

Conclusions: In comparison with hair data obtained under the same environmental conditions, light affected drugs in the hair rather than in nails, whereas water and soil greatly affected drugs in the nails rather than in hair. Although the disposition of drugs incorporated in the tissues differed between nails and hair, the analytes were detected in nails and hair strands left in severe natural environments. MSA could be useful for estimating drug-use histories and personal profiles using the nails and hair of a corpse.

Purpose: Serum caffeine concentration is an indicator of caffeine intoxication; however, it is difficult to measure it in most emergency departments. We developed a simple estimation method using a point-of-care test kit for urinary caffeine.

Methods: Caffeine-spiked human serum (100, 50, 25, and 10 µg/mL) was diluted 10-, 20-, 50-, and 100-fold with phosphate-buffered saline and applied to the kit. After 5 min incubation, the kit was scanned by a flatbed scanner and the membrane image was processed with ImageJ.

Results: When the 20-fold diluted serum was applied, serum samples with initial caffeine concentration ≤ 25 and ≥ 50 µg/mL were caffeine-negative and -positive, respectively. When the 100-fold diluted serum was applied, none of the caffeine-spiked serum samples gave positive results. Therefore, we proposed the following test procedure: (i) 20-fold diluted serum was initially tested and (ii) 100-fold diluted serum was additionally tested when the initial result was caffeine positive. Using this procedure, caffeine concentration is expected to be classified into three levels: ≤ 25, > 25- ≤ 100, and > 100 µg/mL, which almost correspond to no or mild, severe, and potentially fatal intoxication, respectively. The test procedure was validated using postmortem heart blood from two cases of fatal caffeine intoxication (caffeine concentration: 276 and 175 µg/mL) and two cases of other intoxication.

Conclusions: Our developed method using point-of-care urinary caffeine test kits enabled simple estimation of serum caffeine concentration.