RESUMEN
OBJECTIVE: People regularly contact emergency medicine services concerned that they have been exposed to drink spiking, i.e., exposure to drugs without their knowledge or permission. We identified drugs in blood and urine samples from patients suspecting exposure to drink spiking, with special consideration for drugs not reported taken by the patient (unreported drugs). METHODS: From September 2018 to May 2019, we collected blood and urine samples from patients 16 years or older presenting at an emergency clinic in Oslo, Norway, within 48 hours of suspected exposure to drink spiking. We also collected information on ethanol ingestion and drugs taken. Blood samples were analyzed for 20 classical recreational drugs using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and an automated enzymatic method for ethanol. Urine samples were analyzed using immunoassay methods and a specific gas chromatography mass spectrometry (GCMS) method for gammahydroxybutyrate (GHB). RESULTS: From 100 included patients (median age 24 years, 62 females), we collected 100 blood samples and 72 urine samples. Median time since exposure was 5 hours. Unreported drugs were found in 15 patients. Unreported drugs in the blood samples were clonazepam in 3, methylenedioxymethamphetamine (MDMA) in 3, amphetamine in 2, tetrahydrocannabinol (THC) in 2, tramadol in 1, cocaine in 1, and methamphetamine in 1. Unreported drugs in the urine samples were cocaine in 5, amphetamine in 4, ecstasy in 3, and cannabis in 2. Ethanol was found in 69 patients, all reporting ethanol ingestion. Median blood ethanol concentration was higher in patients with no unreported drugs detected, 1.00 (interquartile range (IQR) 0-1.52) vs. 0 (IQR 0-0.46) (p<0.001). GHB was not detected. CONCLUSION: Unreported drugs, possibly used for drink spiking, were found in 15% of patients. Blood ethanol concentration was higher when no unreported drugs were found. GHB was not detected in any patient.
Asunto(s)
Drogas Ilícitas , Detección de Abuso de Sustancias , Espectrometría de Masas en Tándem , Humanos , Noruega/epidemiología , Femenino , Masculino , Adulto , Estudios Prospectivos , Drogas Ilícitas/orina , Drogas Ilícitas/sangre , Adulto Joven , Detección de Abuso de Sustancias/métodos , Espectrometría de Masas en Tándem/métodos , Adolescente , Persona de Mediana Edad , Cromatografía Líquida de Alta Presión , Etanol/orina , Etanol/sangre , Cromatografía de Gases y Espectrometría de Masas/métodosRESUMEN
BACKGROUND: With the decline of the use of ketamine, one of the common drugs of abuse in Hong Kong, detection of ketamine-related analogues in local laboratories has been encountered. AIM: A brief account of the occurrence of fluorodeschloroketamine (FDCK) in forensic cases is reported through a retrospective study of all drug seizures and driving under the influence of drugs (DUID) cases since its first appearance. METHODS: Identification of FDCK in drug seizures was achieved through gas chromatography - mass spectrometry (GC-MS) and/or liquid chromatography - diode array detection (LC-DAD) methods while its quantification was performed using gas chromatography - flame ionization detection (GC-FID). For the analysis of blood samples in DUID cases, identification and quantification were performed using LC-MS/MS by monitoring the respective transitions of FDCK and fluorodeschloronorketamine (FDCNK) using ketamine-d4 and norketamine-d4 respectively as internal standards. RESULTS: Since its first submission in November 2018, a total of 74 drug seizure cases (151 items) and 6 drug driving cases were encountered till December 2019. Drug seizures found with FDCK were physically similar to those of ketamine seizures. The majority of items were detected with FDCK only (103 items, â¼67%) or as a mixture of FDCK with ketamine (42 items, â¼28%). The drug purity detected with either FDCK only or FDCK mixed with ketamine was high which was similar to those purity found in ketamine seizures. The blood drug concentrations of FDCK of the 6 drug driving cases were in the range of <0.002-1.1 µg/mL and other psychoactive drug(s)/metabolite(s) were also identified. Except for one case where the analysis of the metabolite, fluorodeschloronorketamine (FDCNK), was not conducted due to insufficient sample, the FDCK (FDCNK) concentrations in blood found in the 6 cases were <0.002 (0.005), 0.002 (0.002), 0.002 (0.003), 0.02 (0.035), 0.87 (0.44) and 1.1 (not determined) µg/mL. CONCLUSIONS: With the drug seizures found with FDCK resembled in physical appearance with ketamine seizures, users might likely misuse it as ketamine. Though complicated by other drugs found, it is speculated that the two cases with higher concentration of FDCK found in blood (1.1 and 0.87 µg/mL) might have contributed to the impairment observed.
Asunto(s)
Conducir bajo la Influencia , Cromatografía de Gases y Espectrometría de Masas , Drogas Ilícitas , Ketamina , Humanos , Ketamina/análogos & derivados , Ketamina/sangre , Ketamina/análisis , Drogas Ilícitas/sangre , Hong Kong , Estudios Retrospectivos , Cromatografía Liquida , Masculino , Adulto , Detección de Abuso de Sustancias/métodos , Femenino , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
Novel synthetic opioids (NSOs) represent an emerging group of novel psychoactive substances, acting as agonists at the opioid receptors. NSOs include fentanyl-related compounds, e.g. methoxyacetylfentanyl (MeACF), and non-fentanyl analogs, e.g. "U compounds" including U-47700. Here we present three cases of death involving MeACF and U-47700, with particular reference to preliminary data on pharmacokinetics and tissue distribution.After a complete post-mortem examination, general unknown screenings and analysis of drugs of abuse were performed on postmortem samples by immunoassays, gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. To quantify the analytes of interest in post-mortem blood and tissues, the standard addition method was used. A toxicological significance score (TSS), weighing the role of the NSO in each death case, was assigned.Case 1 died at the hospital after consumption of U-47700, methadone (serum levels: 2,600 ng/ml and 37 ng/ml), tilidine and benzodiazepines. In case 2, U-47700 (204 ng/ml) together with methadone (290 ng/ml), flubromazepam (480 ng/ml) and diazepam (300 ng/ml) were detected in peripheral blood. In case 3, methoxyacetylfentanyl (266 ng/ml), furanylfentanyl (4.3 ng/ml) 4-ANPP (15 ng/ml) and alprazolam (69 ng/ml) were quantified in femoral blood. In all cases, the NSO likely contributed to the death (TSS = 3).NSOs appear to be often consumed in the setting of polydrug intoxications, especially in combination with other opioids and benzodiazepines, which often exert synergistic effects. The standard addition method remains the most reliable in post-mortem analysis and toxicological results should always be evaluated together with circumstantial and autopsy data.
Asunto(s)
Fentanilo , Humanos , Fentanilo/análogos & derivados , Fentanilo/envenenamiento , Fentanilo/sangre , Fentanilo/análisis , Masculino , Adulto , Analgésicos Opioides/envenenamiento , Analgésicos Opioides/sangre , Analgésicos Opioides/análisis , Metadona/envenenamiento , Metadona/sangre , Metadona/análisis , Toxicología Forense , Cromatografía Liquida , Benzodiazepinas/sangre , Benzodiazepinas/envenenamiento , Femenino , Persona de Mediana Edad , Cromatografía de Gases y Espectrometría de Masas , Drogas Ilícitas/sangre , Drogas Ilícitas/envenenamiento , Detección de Abuso de Sustancias , BenzamidasRESUMEN
Amphetamine (AMP) and methamphetamine (METH) use is increasing globally. Illegal AMP is generally a racemic mixture, whereas AMP-containing attention-deficit hyperactivity disorder drugs prescribed in Iceland consist of S-AMP. AMP is also a main metabolite of interest after METH intake. Distinguishing between legal and illegal AMP intake is vital in forensic toxicology. A chiral UPLC-MS-MS method was used to determine the enantiomeric profile of AMP and METH in circulation in Iceland by analysing blood samples from drivers suspected of driving under the influence of drugs (DUID) and seized drug samples from 2021 and 2022. All seized AMP samples (n = 48) were racemic, whereas all but one seized METH sample (n = 26) were enantiopure. Surprisingly, a large portion of the enantiopure METH samples was R-METH. DUID blood samples positive for AMP (n = 564) had a median blood concentration of 180 ng/mL (range 20-2770 ng/mL) and a median enantiomeric fraction (EFR) of 0.54 (range 0-0.73), whereas samples positive for METH (n = 236) had a median blood concentration of 185 ng/mL (range 20-2300 ng/mL) and a median EFR of 0.23 (range 0-1). The findings of this study show a significantly lower blood concentration in drivers with only S-AMP detected compared with when the R-isomer is also detected. No significant difference in blood concentration was detected between the sample groups containing S-METH, R-METH or both enantiomers. The occurrence of R-METH in both seized drug samples and DUID cases indicates a change in drug supply and a need for better scientific knowledge on R-METH abuse.
Asunto(s)
Anfetaminas , Metanfetamina , Detección de Abuso de Sustancias , Espectrometría de Masas en Tándem , Humanos , Islandia , Estereoisomerismo , Metanfetamina/sangre , Detección de Abuso de Sustancias/métodos , Anfetaminas/sangre , Conducir bajo la Influencia , Conducción de Automóvil , Toxicología Forense , Drogas Ilícitas/sangre , Anfetamina/sangre , Estimulantes del Sistema Nervioso Central/sangreRESUMEN
New psychoactive substances (NPS) are uncontrolled analogues of existing drugs or newly synthesized chemicals that exhibit psychopharmacological effects. Due to their diverse nature, composition, and increasing prevalence, they present significant challenges to the healthcare system and drug control policies. In response, healthcare system laboratories have developed analytical methods to detect NPS in biological samples. As a Regional Reference Centre, the Sicilian CRQ Laboratory (Regional Laboratory for Quality Control) developed and conducted an External Quality Assessment (EQA) study to assess, in collaboration with the Istituto Superiore di Sanità (ISS), the ability of different Italian laboratories to identify NPS and traditional drugs of abuse (DOA) in biological matrices. Two blood samples were spiked with substances from various drug classes, including synthetic cannabinoids, cathinones, synthetic opiates, and benzodiazepines, at concentrations ranging from 2 to 10â¯ng/mL. The blood samples were freeze-dried to ensure the stability of DOA and NPS. Twenty-two laboratories from the Italian healthcare system participated in this assessment. The information provided by the laboratories during the registration in an in-house platform included a general description of the laboratory, analytical technique, and the chosen panels of analytes. The same platform was employed to collect and statistically analyze the data and record laboratory feedback and comments. The evaluation of the results revealed that the participating laboratories employed three different techniques for analyzing the samples: GC-MS, LC-MS, and immunoenzymatic methods. Approximately 90 % of the laboratories utilized LC-MS techniques. Around 40 % of false negative results were obtained, with the worst results in the identification of 5-chloro AB PINACA. The results showed that laboratories that used LC-MS methods obtained better specificity and sensitivity compared to the laboratories using other techniques. The results obtained from this first assessment underscore the importance of external quality control schemes in identifying the most effective analytical techniques for detecting trace molecules in biological matrices. Since the judicial authorities have not yet established cut-off values for NPS, this EQA will enable participating laboratories to share their analytical methods and expertise, aiming to establish common criteria for NPS identification.
Asunto(s)
Psicotrópicos , Control de Calidad , Detección de Abuso de Sustancias , Psicotrópicos/sangre , Humanos , Detección de Abuso de Sustancias/métodos , Detección de Abuso de Sustancias/normas , Italia , Laboratorios/normas , Drogas Ilícitas/sangre , Drogas Ilícitas/análisisRESUMEN
Drug-impaired driving is an increasing public safety concern across Canada, particularly due to the demonstrated increase in use of recreational drugs such as cocaine. Cocaine is a central nervous system stimulant drug; however, it can impair an individual's driving ability in both the stimulant and crash phases. Despite the scientific consensus regarding cocaine's potential for driving impairment, there is relatively little information available regarding blood concentrations and associated observations of impairment in suspected impaired drivers. Retrospective data analysis was performed to evaluate suspected impaired driving cases in which cocaine and/or benzoylecgonine were detected alone, or in combination with other drugs, in blood and urine samples submitted to the Toxicology Section of the Centre of Forensic Sciences with incident dates between 2021 and 2022. Cocaine and/or benzoylecgonine were detected in 46% (blood) and 66% (urine) of the total impaired driving samples submitted. In 41 cases where cocaine and/or benzoylecgonine were the only drug finding in blood, concentrations of cocaine and benzoylecgonine ranged from 0.0073 to 0.26 mg/L (mean 0.096 mg/L) and 0.13 to 5.3 mg/L (mean 2.1 mg/L), respectively. Driving observations reported by the arresting officer in cases where cocaine and/or benzoylecgonine were the only drug finding in blood and urine included the driver being involved in a collision, the vehicle leaving the roadway, erratic driving and the driver being asleep at the wheel; observations of drug impairment reported by the drug recognition expert at the time of driver evaluation included abnormal speech patterns, poor balance/incoordination, abnormal body movements and the individual falling asleep. The results provide concentrations of cocaine and benzoylecgonine observed in suspected impaired drivers, insight into observations that may be associated with prior cocaine use and additional information to inform on the effects of cocaine on driving.
Asunto(s)
Cocaína , Conducir bajo la Influencia , Detección de Abuso de Sustancias , Cocaína/análogos & derivados , Cocaína/sangre , Humanos , Detección de Abuso de Sustancias/métodos , Ontario/epidemiología , Estudios Retrospectivos , Conducción de Automóvil , Drogas Ilícitas/sangre , Drogas Ilícitas/orina , Trastornos Relacionados con Cocaína/epidemiología , Masculino , Toxicología Forense , Femenino , Adulto , Estimulantes del Sistema Nervioso Central/sangre , Estimulantes del Sistema Nervioso Central/orinaRESUMEN
New psychoactive substances (NPS), like pyrrolidinophenones, are still very present on the illegal drug market. The presented study reports on two members of this substance group, α-pyrrolidinohexanophenone (α-PHP) and α-pyrrolidinoisohexanophenone (α-PiHP), which occurred in forensic routine cases in the last 6 years. α-PHP could be detected predominantly by a validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) method in 33 authentic human plasma samples and α-PiHP in 8. α-PHP concentrations ranged from ca. 0.75 to 128 µg/L (mean: 23.2, median: 16.3) and α-PiHP concentrations from 7.33 to 118 µg/L (mean: 44.7, median: 33.7, quantified via α-PHP). Individuals were predominantly male and middle aged. As different studies have shown, some pyrrolidinophenones are able to cause aggressive behavior. Therefore, we set out to investigate the relation of α-PHP and α-PiHP plasma concentrations and the behavior of the consumers, reported by police and medical experts. Part of the subjects showed aggressive behavior, including agitation and restlessness. Lethargic and unremarkable behavior might be explained by co-consumption of other drugs, such as opiates/opioids, benzodiazepines, pregabalin or alcohol as well as by drug tolerance and subacute effects of stimulants. Multi-drug use could be detected in all cases; also stimulating substances and multiple different pyrrolidinophenones were determined. Nevertheless, users of α-PHP and α-PiHP showed a tendency to act aggressively, possibly triggered by a high selectivity for dopamine transporter inhibition. In accordance, committed offenses were often violent crimes. This might be considered in terms of toxicological assessment of criminal responsibility and driving ability.
Asunto(s)
Pirrolidinas , Detección de Abuso de Sustancias , Espectrometría de Masas en Tándem , Humanos , Detección de Abuso de Sustancias/métodos , Pirrolidinas/sangre , Masculino , Cromatografía Liquida , Femenino , Drogas Ilícitas/sangre , Pirrolidinonas/sangre , Adulto , Toxicología Forense/métodos , Psicotrópicos/sangre , Persona de Mediana EdadRESUMEN
ABSTRACT: We report 8 children younger than 2 years who died from acute illicit fentanyl intoxications in Connecticut between 2020 and 2022.The Connecticut Office of the Chief Medical Examiner (CT OCME) investigates all unexpected, violent, and suspicious deaths in Connecticut. The CT OCME's electronic database was searched for fentanyl deaths by age. All underwent autopsies and toxicology testing.The ages ranged from 28 days to 2 years (mean age, 12 months). The causes of death involved acute fentanyl intoxications with 1 having xylazine, 1 having para-fluorofentanyl, and 1 having cocaine and morphine. All the manners of death were certified as homicide. The postmortem fentanyl blood concentrations ranged from 0.40 to 46 ng/mL. Most of the children were found unresponsive after being put to sleep. Three were co-sleeping with adults (2 in bed; 1 on a recliner). There was a known history of parental/caregiver drug abuse in 7 of 8 of the fatalities.We summarize the key investigative, autopsy, and toxicological findings. As illicit fentanyl use increases, there is a potential for infant exposure and death. The investigation and certification of these deaths and the role of intentional administration versus inadvertent exposure due to caregiver neglect in the context of the certification of the manner of death are described.
Asunto(s)
Fentanilo , Homicidio , Humanos , Fentanilo/envenenamiento , Fentanilo/análogos & derivados , Fentanilo/sangre , Lactante , Masculino , Femenino , Preescolar , Homicidio/estadística & datos numéricos , Recién Nacido , Connecticut/epidemiología , Analgésicos Opioides/envenenamiento , Analgésicos Opioides/sangre , Médicos Forenses , Narcóticos/envenenamiento , Narcóticos/sangre , Drogas Ilícitas/envenenamiento , Drogas Ilícitas/sangreRESUMEN
BACKGROUND: New Psychoactive Substances (NPS) impose a new challenge on the legal and health care system, yet, there is little information available about how new substances spread based on hospitalization of intoxicated patients. The aims of this study were: (i) to investigate the frequency of NPS among suspected drug intoxicated patients, (ii) to study the connection between blood concentration and clinical symptoms, (iii) to determine their half-life with a time-series blood sampling protocol. METHODS: During the observation period, 116 suspected drug intoxicated patients were sampled. The samples were analyzed for alcohol, 20 classical illicit and licit drugs, and for 78 NPS. Clinical symptoms were registered on-site (by the Emergency Medical Services) and (also) at hospital admittance. RESULTS: NPS were detected in 51 patients of which cathinones were found in 4, the synthetic cannabinoids (SCs) 5 F-MDMB-PINACA and 5 F-MDMB-PICA in 23-23, and CUMYL-CH-MEGACLONE in 2 cases. Poison severity scores (PSS) showed mild to moderate intoxications overall. Connection between blood concentration and severity of clinical symptoms were inconclusive. The calculated half-life of 5 F-MDMB-PINACA and 5 F-MDMB-PICA was 2.50 and 2.68 h, respectively. CONCLUSION: The ratio of SCs among the selected intoxicated patients was higher than expected from seizure data which could be the consequence of targeted patient selection. The clinical symptoms and the severity of intoxication cannot be characterized simply by NPS blood levels. The short half-life of SCs can explain the relatively rapid consolidation of intoxication symptoms.HighlightsIn the Budapest region, the majority of hospitalized NPS intoxications was caused by the synthetic cannabinoids 5F-MDMB-PINACA and 5F-MDMB-PICA in 2018-19.No correlation between blood concentration and symptoms severity could be established.The clinical symptoms of synthetic cannabinoid users improved quickly and no ICU treatment was necessary.The half-life of 5F-MDMB-PINACA and 5F-MDMB-PICA was proved to be 2.50 hours and 2.68 hours, respectively.
Asunto(s)
Drogas Ilícitas/sangre , Detección de Abuso de Sustancias , Humanos , Hungría/epidemiologíaRESUMEN
In post-mortem investigations of fatal intoxication, it is challenging to determine which drug(s) were responsible for the death, and which drugs did not. This study aims to provide post-mortem femoral blood drug levels in lethal intoxication and in post-mortem control cases, where the cause of death was other than intoxication. The reference values could assist in the interpretation of toxicological results in the routine casework. To this end, all post-mortem toxicological results in femoral blood from 2011 to 2017 in Western Switzerland were considered. A full autopsy with systematic toxicological analysis (STA) was conducted in all cases. Results take into account the cause of death classified into one of four categories (as published by Druid and colleagues): I) certified intoxication by one substance alone, IIa) certified intoxication by more than one substance, IIb) certified other causes of death with incapacitation due to drugs, and III) certified other causes of death without incapacitation due to drugs. This study includes 1 990 post-mortem cases where femoral blood was analysed. The material comprised 619 women (31%) and 1 371 men (69%) with a median age of 50 years. The concentrations of the 32 most frequently recorded substances as well as alcohol are discussed. These include 6 opioids and opiates, 3 antidepressants, 6 neuroleptics and hypnotics, 1 barbiturate, 11 benzodiazepines (and related drugs), 2 amphetamine-type stimulants, cocaine, paracetamol, and tetrahydrocannabinol (THC). The most common substances that caused intoxication alone were morphine, methadone, ethanol, tramadol, and cocaine. The post-mortem concentration ranges for all substance are categorized as I, IIa, IIb, or III. Statistical post-mortem reference concentrations for drugs are discussed and compared with previously published concentrations. This study shows that recording and classifying cases is time-consuming, but it is rewarding in a long-term perspective to achieve a more reliable information about fatal and non-fatal blood concentrations.
Asunto(s)
Depresores del Sistema Nervioso Central/sangre , Etanol/sangre , Drogas Ilícitas/sangre , Preparaciones Farmacéuticas/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Toxicología Forense , Humanos , Masculino , Persona de Mediana Edad , Cambios Post Mortem , Suiza , Adulto JovenRESUMEN
ABSTRACT: Acetyl fentanyl (AF) is a Schedule I fentanyl analog that has been increasingly seen in heroin and fentanyl polydrug toxicity overdoses in Michigan (MI). Drug users are often unaware of the presence of AF in their drugs because it is often sold mixed into or disguised as heroin. High levels of AF in heroin drug products can cause increased incidence of overdose. This article describes data from a longitudinal opioid surveillance program and details 102 decedents in MI who were found to have evidence of heroin in their postmortem blood. A large portion of these decedents were also found to have evidence of fentanyl and AF. Our data further show significant overlap in incidence rates of AF and heroin-related overdose deaths in several MI counties, suggesting that AF is becoming enmeshed in heroin trafficking. Furthermore, we report unprecedented high incidence rates of AF and heroin-related overdose deaths in Calhoun county, and we propose that it is a high-intensity drug trafficking area. Highways US-131 and US-31 are likely used to transport these drugs. More study is needed into the drug trafficking trends in MI to ascertain drug sources and monitor the ever developing and dangerous polydrug heroin combinations.
Asunto(s)
Analgésicos Opioides/sangre , Tráfico de Drogas , Dependencia de Heroína/mortalidad , Heroína/sangre , Vigilancia de la Población , Adulto , Cromatografía Liquida , Sobredosis de Droga , Femenino , Fentanilo/análogos & derivados , Fentanilo/sangre , Toxicología Forense , Humanos , Drogas Ilícitas/sangre , Masculino , Michigan/epidemiología , Persona de Mediana Edad , Detección de Abuso de Sustancias , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Smoking mixtures containing synthetic cannabinoids (SCs) have become very popular over the last years but pose a serious risk for public health. Limited knowledge is, however, available regarding the acute effects of SCs on cognition and psychomotor performance. Earlier we demonstrated signs of impairment in healthy volunteers after administering one of the first SCs, JWH-018, even though subjective intoxication was low. In the current study, we aimed to investigate the acute effects of JWH-018 on several cognitive and psychomotor tasks in participants who are demonstrating representative levels of acute intoxication. METHODS: 24 healthy cannabis-experienced participants took part in this placebo-controlled, cross-over study. Participants inhaled the vapor of 75 µg JWH-018/kg body weight and were given a booster dose if needed to induce a minimum level of subjective high. They were subsequently monitored for 4 h, during which psychomotor and cognitive performance, vital signs, and subjective experience were measured, and serum concentrations were determined. RESULTS: Maximum subjective high (average 64%) was reached 30 min after administration of JWH-018, while the maximum blood concentration was shown after 5 min (8 ng/mL). JWH-018 impaired motor coordination (CTT), attention (DAT and SST), memory (SMT), it lowered speed-accuracy efficiency (MFFT) and slowed down response speed (DAT). CONCLUSION: In accordance with our previous studies, we demonstrated acute psychomotor and cognitive effects of a relatively low dose of JWH-018.
Asunto(s)
Cannabinoides/toxicidad , Cannabis/química , Disfunción Cognitiva/inducido químicamente , Drogas Ilícitas/toxicidad , Indoles/toxicidad , Naftalenos/toxicidad , Extractos Vegetales/toxicidad , Trastornos Psicomotores/inducido químicamente , Uso Recreativo de Drogas/psicología , Drogas Sintéticas/toxicidad , Administración por Inhalación , Adulto , Atención/efectos de los fármacos , Cannabinoides/administración & dosificación , Cannabinoides/sangre , Cognición/efectos de los fármacos , Disfunción Cognitiva/sangre , Estudios Cruzados , Método Doble Ciego , Femenino , Voluntarios Sanos , Humanos , Drogas Ilícitas/sangre , Indoles/administración & dosificación , Indoles/sangre , Masculino , Naftalenos/administración & dosificación , Naftalenos/sangre , Extractos Vegetales/administración & dosificación , Extractos Vegetales/sangre , Trastornos Psicomotores/sangre , Desempeño Psicomotor/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Memoria Espacial/efectos de los fármacos , Drogas Sintéticas/administración & dosificación , Adulto JovenRESUMEN
New psychoactive substances continue to appear on the drug market. Until recently, new synthetic opioids, which are among the most dangerous new psychoactive substances, primarily encompassed analogs of the potent analgesic fentanyl. Lately, also other new synthetic opioids have increasingly started to surface. This is the first report on the identification and full chemical characterization of brorphine, a novel potent synthetic opioid with a piperidine benzimidazolone structure. A powder, identified as brorphine, was obtained from a patient seeking medical help for detoxification. Brorphine was also found in a serum sample of the patient. Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) identified an exact mass of m/z 400.1020 and 402.1005 for the compound, corresponding to both bromine isotopes. Further chemical characterization was performed by gas chromatography-mass spectrometry, liquid chromatography-diode array detection and Fourier-transform infrared spectroscopy analyses. Finally, the structure was confirmed by performing 1H-NMR and 13C-NMR spectroscopy. In vitro biological activity of brorphine was determined by a cell-based µ-opioid receptor activation assay, resulting in an EC50 of 30.9 nM (13.5 ng/mL) and an Emax of 209% relative to hydromorphone, confirming the high potency and efficacy of this compound. In a serum sample of the patient, brorphine and a hydroxy-metabolite were found using the LC-HRMS screening method. The presence of opioid activity in the serum was also confirmed via the activity-based opioid screening assay. The occurrence of brorphine is yet another example of how the illicit drug market is continuously evolving in an attempt to escape international legislation. Its high potency poses a serious and imminent health threat for any user.
Asunto(s)
Analgésicos Opioides/sangre , Drogas Ilícitas/sangre , Imidazoles/sangre , Piperidinas/sangre , Psicotrópicos/sangre , Analgésicos Opioides/química , Cromatografía Liquida , Drogas de Diseño/análisis , Fentanilo/análogos & derivados , Cromatografía de Gases y Espectrometría de Masas , Humanos , Drogas Ilícitas/química , Imidazoles/química , Piperidinas/química , Psicotrópicos/química , Detección de Abuso de Sustancias , Espectrometría de Masas en TándemRESUMEN
ABSTRACT: Xylazine is an emerging adulterant with fentanyl in fatal drug intoxications, which has public health, safety, and criminal investigative implications. Xylazine is a nonnarcotic sedative used for analgesia and muscle relaxation exclusively in veterinary medicine. Its chemical structure is similar to clonidine and acts as a central α-2 agonist which may cause bradycardia and transient hypertension followed by hypotension. We report the detection of xylazine in 42 deaths in Connecticut from March to August 2019. Xylazine combined with an opioid or stimulant may affect the toxicity of these drugs. Detection of xylazine may help the forensic pathologist distinguish illicit from prescribed fentanyl, and law enforcement agents track the illicit drugs to a specific drug supplier. Because of its lack of response to naloxone, emergency medicine physicians need to be aware of its potential presence as it may affect therapy.
Asunto(s)
Analgésicos Opioides/envenenamiento , Sobredosis de Droga/mortalidad , Fentanilo/envenenamiento , Hipnóticos y Sedantes/sangre , Drogas Ilícitas/envenenamiento , Xilazina/sangre , Accidentes/mortalidad , Adulto , Analgésicos Opioides/sangre , Cromatografía Liquida , Connecticut/epidemiología , Médicos Forenses , Femenino , Fentanilo/sangre , Humanos , Drogas Ilícitas/sangre , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/mortalidad , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
Suspected unnatural or unexpected deaths in the Northern Territory of Australia are reportable to the coroner, and investigation of such cases typically includes a post-mortem examination with comprehensive toxicological screening. An autopsy case series of five Cumyl-PEGACLONE-related fatalities over a recent eighteen-month period is presented. Databases of the Northern Territory coroner's office and the Royal Darwin Hospital Forensic Pathology Unit were searched to identify deaths related to synthetic cannabis use between July 1, 2018 and December 31, 2020. Toxicological analysis was performed at Forensic Science South Australia using a combination of liquid chromatography, gas chromatography and mass spectrometry. Cumyl-PEGACLONE, a synthetic cannabinoid receptor agonist (SCRA) with a gamma-carbolinone core, was detected in five cases (range in post-mortem blood 0.73-3.0 µg/L). Concurrent alcohol use and underlying cardiovascular disease were considered relevant factors in most cases. Toxicological Significance Scoring was carefully considered in all five cases, and in four cases, the presence of Cumyl-PEGACLONE was considered to be highly significant (TSS = 3). Synthetic cannabis use has not previously been identified in Northern Territory drug trends, and only one fatality related to the use of gamma-carbolines was identified in a recent Australia-wide study on synthetic cannabinoid-related fatalities. Deaths related to Cumyl-PEGACLONE use are emerging in the Northern Territory of Australia; this has public health implications. Although the exact mechanism(s) of death related to Cumyl-PEGACLONE are not fully established, this additional descriptive case series reaffirm an association with underlying cardiovascular disease, and suggest that concurrent use with alcohol may be relevant.
Asunto(s)
Cannabinoides/efectos adversos , Drogas Ilícitas/efectos adversos , Psicotrópicos/efectos adversos , Adulto , Asfixia/complicaciones , Australia , Cannabinoides/sangre , Depresores del Sistema Nervioso Central/sangre , Cromatografía Liquida , Enfermedad de la Arteria Coronaria/complicaciones , Médicos Forenses , Etanol/sangre , Cromatografía de Gases y Espectrometría de Masas , Humanos , Drogas Ilícitas/sangre , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Obesidad/complicaciones , Psicotrópicos/sangre , Trastornos Relacionados con Sustancias/complicacionesRESUMEN
Forensic post-mortem toxicological data provide valuable information for the elucidation of cause of death. However, this is still not routine practice in Brazilian laboratories. This study investigated the presence of illicit and prescription drugs, pesticides and metabolites in 111 post-mortem blood samples from cases investigated by the Forensic Medical Institute of the Federal District, Brazil. Quantitative analysis was performed for 14 analytes using a validated programmed temperature vaporisation-large volume injection-gas chromatography-mass spectrometry method, which was also used as screening (qualitative analysis) for an additional 19 substances of forensic interest. At least one analyte was found in 61.2% of the samples, of which 34 were related to homicide, 15 to accidental death and 10 to suicide cases. The victims were 14-72 years old. The benzodiazepines diazepam, midazolam and 7-aminoflunitrazepan were detected in 46% of the positive samples (0.02-1.12 µg/mL; midazolam only qualitative). Cocaine was found in 34% (0.02-4.07 µg/mL), associated with substances commonly used as cocaine adulterants (e.g. caffeine, lidocaine and phenacetin). Three suicide cases involved the illegal rodenticide chumbinho, residues of which were found in the gastric content, and blood samples showed the presence of terbufos (0.03 and 0.04 µg/mL) and carbofuran (27.3 µg/mL). These results are discussed, along with autopsy and crime-scene information.
Asunto(s)
Análisis Químico de la Sangre , Toxicología Forense , Drogas Ilícitas/sangre , Plaguicidas/sangre , Medicamentos bajo Prescripción/análisis , Adolescente , Adulto , Anciano , Brasil , Causas de Muerte , Femenino , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
A study was undertaken of all drowning deaths that occurred over a 30-year period from 1988 to 2017 in the urban section of the River Torrens, Adelaide, South Australia, an augmented waterway that runs through the central business district. Autopsy records from Forensic Science South Australia (FSSA) were reviewed. There were 34 drownings (0-5 cases/yr) with 28 males and 6 females (M;F = 4.6:1), with an age range for males of 18-76yrs (mean 42.0; SD 18.0) and for females of 20-84yrs (mean 69.3; SD 24.5). There were 15 (44%) accidents, 11 (32%) suicides, 1 (3%) homicide and 7 (21%) undetermined. Of the 22 cases during or after 1994 with complete toxicology reports, 10 (45%) had a blood alcohol concentration (BAC) of greater than 0.05% (g/100 mL) with an illicit substance detected in 4 (18%) cases: (MDMA (3,4-methylenedioxymethamphetamine), methylamphetamine and THC (delta-9-tetrahydrocannabinol) acid). The presence of various therapeutic drugs was also detected in 10 cases (45%) including temazepam, fluoxetine, diazepam, olanzapine, amitriptyline, carbamazepine, codeine, citalopram and valproate. Although the numbers of cases were not high, the urban portion of the River Torrens had a much higher number of drowning events per kilometre compared to other inland waterways in South Australia such as the Murray River. This is most likely due to the vulnerability that exists for intoxicated individuals in the city from falls into the water and to the availability of the river as a means of suicide to members of the adjacent urban population.
Asunto(s)
Ahogamiento/epidemiología , Ciencias Forenses , Ríos , Población Urbana/estadística & datos numéricos , Accidentes/estadística & datos numéricos , Adolescente , Adulto , Australia/epidemiología , Ahogamiento/etiología , Femenino , Homicidio/estadística & datos numéricos , Humanos , Drogas Ilícitas/sangre , Masculino , Persona de Mediana Edad , Psicotrópicos/sangre , Detección de Abuso de Sustancias , Suicidio/estadística & datos numéricos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: The objective of the current study is to determine how alcohol and illicit substance use contributes to motorcycle crash fatalities by examining the relationship between toxicology levels found postmortem and the behavior of riders and passengers in fatal motorcycle crashes. MATERIALS AND METHODS: All motorcycle fatalities in Miami-Dade County, FL, from 2009 to 2014 were reviewed using the Miami-Dade County Medical Examiner's toxicology reports and the corresponding crash reports. RESULTS: Positive alcohol/illicit substance detection was found in 44% of our population of 227 fatalities. When compared with those with a negative alcohol/illicit substance detection, those with a positive alcohol/illicit substance detection were more likely to be found at fault of the crash (77% versus 50%, P < 0.001), more likely to be in a single-vehicle crash (47% versus 21%, P < 0.001) and less likely to wear a helmet (44% versus 64%, P = 0.002). However, there was no significant relationship between speeding and alcohol/illicit substance detection (29% versus 33%, P = 0.748). In addition, a regression analysis demonstrated that there was less helmet use and more single-vehicle crashes with higher blood alcohol concentration. CONCLUSIONS: In fatal motorcycle crashes, alcohol and illicit substance use had a significantly negative impact on the risk aversion of motorcycle fatalities in regard to fault, helmet use, and single-vehicle crashes.
Asunto(s)
Accidentes de Tránsito/mortalidad , Conducir bajo la Influencia/estadística & datos numéricos , Motocicletas , Detección de Abuso de Sustancias/estadística & datos numéricos , Trastornos Relacionados con Sustancias/diagnóstico , Adulto , Nivel de Alcohol en Sangre , Etanol/sangre , Etanol/orina , Femenino , Dispositivos de Protección de la Cabeza/estadística & datos numéricos , Humanos , Drogas Ilícitas/sangre , Drogas Ilícitas/orina , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trastornos Relacionados con Sustancias/sangre , Trastornos Relacionados con Sustancias/orina , Adulto JovenRESUMEN
Driving under the influence of drugs (DUID) is a serious global problem and poses a public health risk. With new psychoactive substances (NPS) entering the illicit drug market several years ago, a significant number of highly potent and harmful drugs have become easily available and the use of these substances may impair a person's ability to drive a vehicle safely. Since NPS are not usually covered in routine toxicological analyses used in DUID investigations, only little is known about their prevalence. To gather more information on the prevalence of NPS in cases of impaired driving, a retrospective study was conducted to determine the prevalence of these drugs in blood samples of DUID suspects in southern Germany. A total of 837 blood samples, which were collected in the German federal states Baden-Württemberg and Bavaria in 2017 and 2018, were reanalyzed for designer stimulants and synthetic cannabinoids by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). For the analysis of synthetic cannabinoids, a more sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening method was additionally used. A total of 14 cases (1.6%) tested positive for NPS. Designer stimulants were detected in two cases (0.2%) and synthetic cannabinoids were found in 12 cases (1.4%). The rather low prevalence rate of 1.6% estimated in this study suggests that driving under the influence of NPS does not play a large role in southern Germany. Nonetheless, in all cases in which the psychophysical impairment cannot be explained by routine toxicological findings, a screening for NPS should additionally be performed.
Asunto(s)
Conducir bajo la Influencia , Drogas Ilícitas/sangre , Psicotrópicos/sangre , Detección de Abuso de Sustancias , Adulto , Alemania , Humanos , Estudios Retrospectivos , Adulto JovenRESUMEN
PROBLEM: The problem of impaired driving is well documented in the literature but is heavily dependent upon self-report studies and/or databases that do not include in-depth information about the contributing origins of fatalities. AIM: This study aimed to conduct an in-depth analysis of Coroner's findings for all fatally injured drivers in the state of Queensland in order to explore the prevalence of alcohol and different types of illicit substances (including drug combinations) in fatal crash reports. METHOD: A total of 701 Coroner's reports related to drivers or controllers of vehicles involved in traffic related fatalities for the period of 2011-2015 were analysed, revealing 306 controllers (43.6%) were detected with either alcohol or illegal drugs (e.g., methylamphetamine, Δ9-tetrahydrocannabinol, cocaine or MDMA) RESULTS: Alcohol was the most commonly detected substance identified with 223 cases (72.9% of the drug and alcohol sample). Illicit drug detections totalled 147 cases (48% of the drug and alcohol sample) with Δ9-tetrahydrocannabinol the most commonly detected illicit substance (109 cases; 35.6% of the drug and alcohol sample) followed by methylamphetamine (total of 63 cases; 20.6% of the drug and alcohol sample). An important theme to emerge was the prevalence of polysubstance use among fatally injured drivers, not just for alcohol and one drug type, but also multiple drug combinations. Fatality trends revealed a decrease in both non-substance and alcohol-related fatalities across the study period. However, road fatalities where an illicit substance was detected increased by approximately 57%. Males were overrepresented as a proportion of total fatalities (82.4%) and there were no significant sex or age differences regarding illicit substance related deaths. Drivers of passenger vehicles were most commonly identified in the data (66.2%), but motorcycle operators were disproportionately represented (28.1% of the total controller sample compared to 4% of vehicle registrations in Queensland) CONCLUSION: This case study analysis of fatal crashes not only confirms the ongoing problem of alcohol and driving, but also illuminates the emerging (and escalating) issue of illicit substances detected in fatally injured drivers.