Forensic Toxicology最新文献

Purpose: JWH-424, (8-bromo-1-naphthyl)(1-pentyl-1H-indol-3-yl)methanone, is a synthetic cannabinoid, which is a brominated analogue of JWH-018, one of the best-known synthetic cannabinoids. Despite the structural similarity to JWH-018, little is known about JWH-424 including its metabolism. The aim of the study was to compare human liver microsomes (HLM) and the fungus Cunninghamella elegans as the metabolism catalysts for JWH-424 to better understand the characteristic actions of the fungus in the synthetic cannabinoid metabolism.

Methods: JWH-424 was incubated with HLM for 1 h and Cunninghamella elegans for up to 72 h. The HLM incubation mixtures were diluted with methanol and fungal incubation mixtures were extracted with dichloromethane and reconstituted in methanol before analyses by liquid chromatography-high-resolution mass spectrometry (LC-HRMS).

Results: HLM incubation resulted in production of ten metabolites through dihydrodiol formation, hydroxylation, and/or ipso substitution of the bromine with a hydroxy group. Fungal incubation led to production of 23 metabolites through carboxylation, dihydrodiol formation, hydroxylation, ketone formation, glucosidation and/or sulfation.

Conclusions: Generally, HLM models give good predictions of human metabolites and structural analogues are metabolised in a similar fashion. However, major hydroxy metabolites produced by HLM were those hydroxylated at naphthalene instead of pentyl moiety, the major site of hydroxylation for JWH-018. Fungal metabolites, on the other hand, had undergone hydroxylation mainly at pentyl moiety. The metabolic disagreement suggests the necessity to verify the human metabolites in authentic urine samples, while H9 and H10 (hydroxynaphthalene), H8 (ipso substitution), F22 (hydroxypentyl), and F17 (dihydroxypentyl) are recommended for monitoring of JWH-424 in urinalysis.

Purpose: The aim of this study is to investigate the stabilities of the 24 synthetic cannabinoid metabolites (SCMs) in blood and urine at various temperatures from - 30 to 37 ℃ stored for 1-168 days. In addition, experiments of stabilities at lower temperatures and for much longer duration have been performed as described below.

Methods: The quantification was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The blank blood and urine spiked with SCMs and non-spiked real case (authentic) specimens were incubated at 37 ℃ up to 56 days and at 22, 4 or - 30 ℃ up to 168 days. The non-spiked authentic blood and urine specimens were also stored at - 30 or - 80 ℃ for 1, 3 or 5 years to investigate stabilities during very long time frames.

Results: All the 24 SCMs were much more stable in urine than in blood at 37, 22 or 4 ℃. All 24 SCMs spiked into blood or urine were stable at - 30 ℃ for up to 168 days. The 6 SCMs in the authentic specimens exhibited long stabilities at - 30 or - 80 ℃ for 3-5 years. Some tendencies were observed according to the relation between the structures of SCMs and their stabilities.

Conclusions: The long-term stabilities of 24 SCMs in spiked samples and those of 6 SCMs in the authentic specimens were examined using LC-MS/MS. SCMs were largely very stable and usable several years after storage at - 30 or - 80 ℃.

Purpose: Death related to the use of drugs is evident when drugs are detected in biological matrices within toxic levels, but sometimes it can be less obvious. Intoxications after 2,5-dimethoxy-4-chloroamphetamine (DOC) use are occurring but up to date, only one fatality has been reported. Here we present the case of a young woman admitted to hospital as she presented vomiting, convulsions and cardiorespiratory arrest.

Methods: Blood ethanol concentration was determined using gas chromatography with flame ionization detection and toxicological screenings (blood, gastric content and hair samples) were performed using liquid chromatography with diode array detection, gas chromatography or liquid chromatography with mass spectrometry detection.

Results: Her health state declined with cardiac troubles, organs failure and cerebral edema till death occurring 4 days later. The autopsy revealed the presence of hemorrhagic infiltration inside the left ventricle, pulmonary edema and hemorrhagic infiltration of the terminal ileum. The analysis of biological fluids confirmed the presence of DOC (< 10 ng/mL in cardiac blood sample), buprenorphine, cocaine and cannabis metabolites. The analysis of hair highlighted a history of drugs abuse.

Conclusion: In the absence of evident identified cause, the hypothesis of a death due to acute drugs use within a history of chronic consumption of drugs has been put forward. The concentration of some substances such as new psychoactive substances can be low in biological matrices but the toxic effects can be additive and lead to death even within young people, hence the importance of the knowledge of consumption history.

Purpose: Since the 1980s, the detection sensitivity of mass spectrometers has increased by improving the analysis of drugs in hair. Accordingly, the number of hair strands required for the analysis has decreased. The length of the hair segment used in the analysis has also shortened. In 2016, micro-segmental hair analysis (MSA), which cuts a single hair strand at a 0.4-mm interval corresponding to a hair growth length of approximately one day, was developed. The advantage of MSA is that the analytical results provide powerful evidence of drug use in the investigation of drug-related crimes and detailed information about the mechanism of drug uptake into hair. This review article focuses on the MSA technique and its applications in forensic toxicology.

Methods: Multiple databases, such as SciFinder, PubMed, and Google, were utilized to collect relevant reports referring to MSA and drug analysis in hair. The experiences of our research group on the MSA were also included in this review.

Results: The analytical results provide a detailed drug distribution profile in a hair strand, which is useful for examining the mechanism of drug uptake into hair in detail. Additionally, the analytical method has been used for various scenarios in forensic toxicology, such as the estimation of days of drug consumption and death.

Conclusions: The detailed procedures are summarized so that beginners can use the analytical method in their laboratories. Moreover, some application examples are presented, and the limitations of the current analytical method and future perspectives are described.

Purpose: Since the appearance of fentanyl followed by its many kinds of analogues around 1988, North America has been exposed to fierce synthetic opioid pandemic resulting in more than 130,000 deaths due to their overdoses until May 2019, when China declared to prohibit the licit fentanyl analog production. However, the Chinese announcement did not go into force in USA due to the adroit strategies of tough traffickers. Thus, contrary to the expectation, the number of synthetic opioid products and their poisoning cases in USA has increased by about 30%; especially, various benzimidazole synthetic opioids have revived on the illicit drug market during a recent few years. In this article, the recent abrupt changes in the situations of illicit synthetic opioid market and their current abuses are described.

Methods: Various databases, such as SciFinder, Google, and Google Scholar, were utilized to collect relevant reports referring old but newly appearing synthetic opioids.

Results: At the present time, there are several families of new synthetic opioids, which are not fentanyl derivatives; MT-45 and its analogs, benzamide and 2-phenylacetamide opioids (U-series opioids), and benzimidazole opioids. Most of the above substances had been developed in 1950s to 1970s, but had never been used as analgesic medicines, because of their severe adverse effects, such as respiratory depression, physical dependence, and resulting deaths. However, there is possibility that these drugs will become main illicit synthetic opioids in place of the fentanyl analogs during coming several years from this time.

Conclusions: All of the above non-fentanyl-derived families had been developed 50-70 years ago to establish them as analgesic medicines, but had been unsuccessful. These drugs largely appeared in the illicit drug markets in North America, Europe, and Australia, during recent years. Pharmacological, toxicological, and metabolic studies are insufficient for benzamide and 2-phenylacetamide opioids, and are very scant especially for benzimidazole opioids. This time we should start studying pharmacotoxicology of the newly emerging synthetic opioids to alert forensic toxicologists in the world and to suppress their rapid and wide spread in the world.

Purpose: Prevalence measures of sociological interest concerning cocaine presence on banknotes are fraught with (i) the extreme variability of its concentration (seven orders of magnitude); (ii) the high number of banknotes needed for the statistical significance. Banknote dust from counting machines from a large and representative number of banknotes in circulation in a specific area represents the most eligible sample to ascertain cocaine circulation. No chromatographic method is available in this respect. This study aims at developing the first analytical methodology for the determination of cocaine in banknote dust samples.

Methods: This novel and straightforward approach consists of a simple methanol extraction followed by analytical determinations via ultra-high performance liquid chromatography coupled to Orbitrap high-resolution mass spectrometry.

Results: Satisfactory analytical performance was obtained with a coefficient of determination of 0.996; maximum within-run and between-run precisions were, respectively, 1.85% and 5.20%. Limits of detection and quantification were, respectively, 3 and 9 ng/mL with an overall process efficiency of 93.2%. The method developed was successfully applied to 9 banknote dust samples from local banknote counter machines. The found concentrations ranged from 2.18E + 02 to 2.31E + 03 μg of cocaine per gram of banknote dust and varied only one order of magnitude, much less than cocaine concentration on banknotes.

Conclusions: To have an idea of cocaine circulation in a geographical area, the sampling of banknote dust, compared to banknotes, consists of tremendous advantages in terms of statistical significance, higher cocaine concentrations, and lower variability: this is crucial from the sociological point of view.

This study aimed to compare whole blood and serum concentrations of quetiapine in acute poisoning cases. Authentic whole blood and respective serum samples were routinely collected from patients diagnosed with blood poisoning at our University Hospital. Accordingly, whole blood and serum paired samples from nine patients (one male and eight female patients) were analyzed for quetiapine using liquid chromatography-mass spectrometry (LC-MS). Quetiapine concentrations in whole blood and serum samples ranged widely from 5.4 to 2780 ng/mL and 9.9 to 2500 ng/mL, respectively. The whole blood/serum concentration ratio was 0.5-1.1 and increased together with an increase in whole blood and serum quetiapine concentrations. The ratio was reversed at around 2500 ng/mL to > 1. Our findings suggest that whole blood concentrations are more useful than serum concentrations in diagnosing quetiapine poisonings.