The use of new psychoactive substances (NPS) has rapidly increased over the last decade. In the last 4 years, producers increasingly appear to be targeting non‐controlled synthetic opioids, involving ...fentanyl derivatives such as ocfentanil (OcF). Identification of metabolites is of major importance in the context of NPS use, as it could improve the detection window in biological matrices in clinical and forensic intoxication cases. Hence, this work aims to report a fatality involving OcF documented by the identification of metabolites. A 30‐year‐old woman was found dead at home: an unidentified powder was found near her body and some injection sites were found at the autopsy. Toxicological analyses allowed to determine the presence of OcF in the powder, blood (3.7/3.9 μg/L, peripheral/cardiac) and in other post‐mortem samples. The most relevant potential CYP‐ and UGT‐dependent metabolites of OcF were investigated in vitro using human liver microsome incubation and liquid chromatography coupled with high resolution mass spectrometry, and subsequently confirmed in post‐mortem samples. Four OcF metabolites were produced in vitro (a mono‐hydroxylated OcF, O‐desmethylOcF, a hydroxylated desmethylOcF and a glucuronidated form of the O‐desmethylOcF), and all except the glucuronide were observed in blood and bile post‐mortem samples. Considering the relative intensity of the chromatographic peak areas, O‐desmethylOcF can be suggested to be an abundant metabolite of OcF. Nevertheless, the relevance of O‐desmethylOcF as being a complementary analytical target of OcF for OcF use detection needs further in vivo confirmation, especially through analysis of urines from users.
This work reports a fatality involving ocfentanil (OcF), a fentanyl derivative, documented by the identification of OcF metabolites. CYP‐ and UGT‐ dependent metabolites of OcF were in vitro investigated using human liver microsome incubation and liquid chromatography with high‐resolution mass spectrometry detection, and subsequently confirmed in post‐mortem samples. Four OcF metabolites were in vitro produced (including O‐desmethylOcF as suggested most abundant metabolite of OcF) and all except one were observed in blood and bile post‐mortem samples.
3-methylmethcathinone (3-MMC) has been available on the European drug market for several years, but an increase in its availability seems to have occurred around 2020, associated with reports of harm ...and death. We aimed to analyze the composition of the supposed 3-MMC samples purchased and its concordance with the assumed composition of the drug.
A prospective multicenter (n = 6) study was conducted between February 2021 and September 2021 in Auvergne-Rhone-Alpes, France. The inclusion criteria were: 3-MMC users over 18 years of age in contact with a community-based organization (CBO) called AIDES. Consumption was evaluated with an anonymized questionnaire and samples of 3-MMC powder were analyzed with a combination of qualitative (GC-MS) and quantitative methods (UPLC-MS/MS), to compare the assumed and real compositions of the products purchased.
We studied 45 samples provided by 33 users. The study population was predominantly male (91%), with a median age of 40 years, most were university graduates and regular users of 3-MMC. Intravenous drug use was reported by 15.2% of the population. Most of the users bought their 3-MMC online via the Clear Web. Drug testing was requested by 86% of the users, highlighting the need for this type of harm reduction strategy. The purity of the 3-MMC powder samples tested ranged from 21 to 98%. Other NPS drugs, such as 4-CEC (4-chloroethcathinone), 4-MMC, and 2-fluorodeschloroketamine (2-FDCK), supplied as methoxphenidine (MXP), were also detected.
This prospective study shows that 3-MMC purity and dose vary considerably. It also describes the characteristics of 3-MMC users and their expectations of a drug-checking program. Our data suggest that drug-checking services may be useful in this population. Health associations and laboratories should work together to help increase access to such programs.
Homicidal poisonings remain rare and can be difficult to detect, especially in the elderly or in medical settings. In this atypical poisoning series, a young nursing assistant purposely poisoned ...thirteen residents of a nursing home and killed ten of them. The medications used were a mix of psychotropic medications (cyamemazine, loxapine, tiapride, risperidone, and mirtazapine), under liquid formulation, which were inducing malaise and coma. The forensic investigation included analysis of blood, urine, hair, and bone marrow and exhumations of seven corpses up to 3 years after the inhumation. Hair collected from a hairbrush of a cremated victim have been analyzed. Bone marrow sample preparation was based on a liquid/liquid triple extraction. Hair were incubated after decontamination overnight at 55 °C in methanol. Segmentation was possible for seven samples, except for delayed exhumation samples (
n
= 4) and hairbrush hair sample (
n
= 1). The extracts were then analyzed using gas chromatography coupled with mass spectrometry (GC–MS) for unknown screening and using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) for a targeted screening and quantification. Screenings revealed the presence of the same mix of psychotropic medications. Cyamemazine, mirtazapine, loxapine, tiapride, and risperidone hair concentrations were 6–17,458 pg/mg, 74–1271 pg/mg, 9–1346 pg/mg, 13–148 pg/mg, and 3–5 pg/mg, respectively. Cyamemazine bone marrow concentrations were 229 and 681 ng/g and 152–717 ng/mL in blood. Patients’ medications were also identified and quantified. This poisoning series provide analytical data that could support subsequent toxicological result interpretation in similar forensic cases.
Le rôle des molécules GABAergiques dans la toxicologie médico-légale en France dépend de ses différents domaines d’investigations. Si la prevalence du GHB/GBL, du baclofène et de la prégabaline est ...très faible dans les décès directement liés aux toxiques, il faut rester vigilant et les rechercher systématiquement dans le cadre de « l'expertise toxicologique de référence » car de nouveaux usages peuvent être individuellement dramatiques, comme le montrent les quelques cas annuels mortels. La prévalence des GABAergiques classiques que sont l’alcool et les benzodiazépines et apparentées reste en revanche élevée dans les décès toxiques mais le plus souvent associés à d’autres substances psychoactives. Toutes les molécules GABAergiques sont susceptibles de modifier le comportement. Dans la conduite automobile, l’alcool est systématiquement recherché, à raison, puisqu’il reste impliqué dans 30 % des accidents mortels. En revanche, l’implication des benzodiazepines et apparentés est mal décrite malgré une consommation importante, par absence d’analyse systématique. Dans d’autres situations médico-légales telles que les accidents du travail ou les faits de violence, l’expert toxicologue est également sollicité puisque l’éthanol et les médicaments psychoactifs font souvent partie des toxiques à rechercher. Enfin, dans le domaine de la soumission chimique, les molécules GABAergiques sont prioritairement impliquées puisque ce sont les benzodiazépines ou apparentés qui se disputent toujours le trio de tête depuis de nombreuses années dans les molécules répertoriées par les enquêtes nationales annuelles.
The role of GABA agonists in forensic toxicology in France depends on its different areas of investigation. If the prevalence of GHB / GBL, baclofen and pregabalin is very low in toxic deaths, it is necessary to remain vigilant and to screen it systematically within the context of toxicological expertise because new uses can be individually dramatic as shown by the few annual fatal cases. However, the prevalence of conventional GABA agonists like alcohol and benzodiazepines remains high in toxic deaths, but is most often associated with other psychoactive substances. All GABA agonists can modify behavior. In driving, alcohol is always analyzed since it remains involved in 30 % of fatal accidents. In contrast, the involvement of benzodiazepines and Z-drugs is not well described, despite significant consumption, due to a lack of systematic analysis. In other forensic situations such as workplace accidents or acts of violence, toxicologists are also solicited to analyze ethanol and psychoactive drugs. Finally, in the field of Drug-facilitated crime GABA agonists are mainly involved because benzodiazepines or Z-drugs have for many years been in the top trio of substances listed in the annual national surveys.
Driving under the influence of drugs (DUID) is a risk factor for traffic accidents. The testing of oral fluid by roadside immunochromatography and laboratory-confirmed chromatography coupled to mass ...spectrometry (LC-MS/MS) analysis to detect drug abuse has increased in France. The aim of this study was to describe the trends observed in drivers testing positive for illicit drugs in oral fluid and to investigate the concordance between the two analytical methods used.
We received for confirmation 3051 oral fluid samples from drivers who had tested positive at the roadside with a Drugwipe-5S® device between 2018 and 2021 around Grenoble, France. Samples were collected with FLOQSwab® and analyzed by LC-MS/MS (THC, amphetamine, methamphetamine, MDMA and MDA, MDEA, cocaine and benzoylecgonine, morphine and 6-monoacetylmorphine) at Grenoble Alpes University Hospital, France. Binomial logistic regression was performed to evaluate consumption trends.
Most of the drivers were men (93.2%), with a median age of 26 years (range: 14–66 years). Cannabis (94.6%) cocaine (17.5%) and MDMA (2.5%) were the drugs most frequently detected. Poly-drug use was observed in 17.3% of drivers and involved cannabis and cocaine in 85.3% of these drivers. Poly-drug use was more frequent among drivers over the age of 32 years (OR, 3.48; 95% CI, 2.59–4.68; p ≤ .001), as was cocaine use (OR, 5.15; 95% CI, 3.75–7.08; p ≤ .001). The frequency of positive tests for amphetamines was higher in women than in men (OR, 2.53; 95% CI, 1.50–4.27; p ≤ .001). The positive predictive value of Drugwipe-5S was 98.2% for cannabis, 22.6% for amphetamines, 75.4% for cocaine and 17.3% for opiates. At least one discrepancy between Drugwipe-5S® and LC-MS/MS results was observed for 22.3% of the samples tested.
We report recent trends for drivers testing positive for illicit drugs in oral fluid in France. Cannabis was the most prevalent drug of abuse identified, suggesting that a general prevention program might be useful. Our results also highlight the need for LC-MS/MS confirmation when screening oral fluid for drugs of abuse.
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•Poly-drug use was observed in 17.3% of drivers who tested positive to DrugWipe-5S.•85.3% of poly-drug consumptions were an association of cannabis and cocaine.•Cocaine and poly-drug use were more frequent among drivers older than 32 years-old.•22.3% of OF samples had discrepancies between Drugwipe-5S® and LC-MS results.•A targeted prevention program may be useful in driver subgroups.
•- Chemical submission can affect victims of all ages not only youngest.•- Toxicological analyzes using appropriate methods are mandatory for diagnosis.•- The name “date-rape drug” is wrongly ...attributed to GHB (less than 4% of our cohort)•- Benzodiazepines deserve this naming due to their highest prevalence each year.
Drug facilitated-crime or chemical submission (DFC/CS) is defined as the concealed or forced administration of psychoactive substances to a victim for criminal purposes. This is a national program set up in the early 2000s in the form of a prospective multicenter survey, the results of which this manuscript presents. Over this 19-year period, 5487 cases were collected, analyzed and classified into 54% of suspected cases, 29% of chemical vulnerability (CV) cases and 17% of proven DFC/CS cases. In the overall data, the most prevalent victims were female (81%), with an average age of 27 years. Sexual assault was the most frequent aggression (77%), followed by theft (14%).
Victims of proven DFC/CS cases were from of all ages including children and elderly. In 934 victims of DFC/CS, 100 various psychoactive substances were detected mostly represented by benzodiazepines and z-drugs (55%), various sedatives including antihistamines (16%) and non-therapeutic substances (16%). Gamma-hydroxybutyric acid (GHB) was found in 4% cases. In CV cases, alcohol (90%) and cannabis (32%) intake were mainly involved
In France, despite prevention messages, DFC/CS has been an epidemic for many years and has been proven by our national study. This national program has the aim to identifying the substances used but unfortunately not the goal to fight against this phenomenon. Since 2009, we observed a new modus operandi of the aggressors who pose as taxi drivers facilitating the reception of the victims leaving nightclubs. We can emphasize that GHB is not the “date rape drug” but rather the benzodiazepine class is.
Purpose
Since the early 2010s, deaths due to the use of new synthetic opioids (NSO) including fentanyl and its analogs have been increasing dramatically. As fentanyl analogs bear strong structural ...similarities, they can share common metabolites. In some clinical or forensic cases, it can be important to demonstrate the presence of both the metabolite and the parent product to confirm that the compound is responsible for the intoxication. Norcarfentanil is a common metabolite of carfentanil (NSO) and remifentanil (widely used in medical care). This article reported the investigation of norcarfentanil origin in three cases.
Methods
Comprehensive screenings were performed using gas chromatography coupled to mass spectrometry and liquid chromatography coupled to a diode array detection, whereas targeted screening of NSO were performed using liquid chromatography coupled to tandem mass spectrometry.
Results
Norcarfentanil was detected at concentrations ranging from 0.05 to 15.8 ng/mL in plasma and from 8.8 to 1820 ng/mL in urine, but carfentanil was detected in two out of the three cases. The presence of norcarfentanil has been supposed to be due to the treatment with remifentanil during the medical care of the patient.
Conclusions
In the first two cases, norcarfentanil was present as the metabolite of carfentanil, whereas in the last case, norcarfentanil was the metabolite of remifentanil. Without the identification of remifentanil, confusion could occur, and norcarfentanil could be attributed to carfentanil misuse.
A middle-aged woman was found dead with multiple empty blisters of midazolam (MDZ) (DORMICUM®), equivalent to 450 mg, near her body. The autopsy revealed that the cause of death was secondary to an ...asphyxia syndrome. Standard toxicological procedures identified MDZ only in blood, urine and gastric content. A quantitative analytical method for MDZ and 1-hydroxymidazolam (1-OH-MDZ) was validated using protein precipitation, a phospholipid removal Ostro® plates and liquid chromatography coupled to tandem mass spectrometry. MDZ and 1-OH-MDZ were quantified in peripheral blood at 910 and 534 ng/mL, respectively, and superior to 2000 ng/mL in urine. Reported to the body weight, the dose, which was lethal, was estimated to be 6.7 mg/kg. The usual dose used in the intensive care unit is 0.03-0.3 mg/kg. MDZ intoxication outside of hospital is rare given the restricted availably of this drug in France. Nevertheless, MDZ under oral form remains available in several countries. Toxic MDZ blood concentrations are described after intravenous administration for anesthesia and are not suited for oral intoxication. Based on the autopsy findings, police investigation and toxicology results, the cause of death was determined to be a self-inflicted oral MDZ acute intoxication, which is the first to be documented to the best of our knowledge. This fatal intoxication provides analytical data that could support subsequent toxicological result interpretation in similar forensic cases.
Highlights • Case report of a baby intoxication with amitriptyline. • Interpretation difficulties in hair testing, particularly in children are discussed. • Interest of complement hair testing in ...child, family members and close circle. • Rapid LC–MS/MS method with automated online sample clean-up. • Quantification of AMI and NOR in hair from small amount of sample.
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