Intoxications involving methoxyacetylfentanyl and U-47700: a study of 3 polydrug fatalities.

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.

A Series of 8 Illicit Fentanyl Intoxication Deaths in Infants and Toddlers.

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.

Technical and health governance aspects of the external quality assessment system for classical and new psychoactive substances analysis testing in blood.

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 10 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.

Enantiomeric profile of amphetamines in seized drug samples and in blood of impaired drivers in Iceland: The rise of (R)-methamphetamine?

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.

α-Pyrrolidinohexanophenone (α-PHP) vs. α-pyrrolidinoisohexanophenone (α-PiHP): A toxicological investigation about plasma concentrations and behavior in forensic routine cases.

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.

Fluorodeschloroketamine found as a street drug in drug seizures and drug driving cases in Hong Kong.

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, ∼67%) or as a mixture of FDCK with ketamine (42 items, ∼28%). 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.

A two-year review of cocaine findings in impaired driving investigations in Ontario, Canada.

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.

Drugs in blood and urine samples from victims of suspected exposure to drink spiking: A prospective observational study from Oslo, Norway.

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.

Testing for Drugs of Abuse: Part 1

Drugs of abuse are commonly encountered in the workplace and the occupational health specialist is often asked to perform and interpret tests to check for the presence of such substances. A clear understanding regarding the limitations of testing is required for this purpose as this field has many potential pitfalls. This is the first of two articles that provide a broad overview of the commonly encountered drugs of abuse (DOA); the biological samples that can be used; possible interferants and adulterants that may be encountered; and the role of the laboratory and pathologist. The second article in this series examines the technology involved; looking briefly at immunoassays and mass spectrometry; and issues regarding cut-points and interpretations

Consumo de sustancias y suicidios en México: resultados del sistema de vigilancia epidemiológica de las adicciones, 1994-2006 / Substance use in suicides in Mexico: results of the epidemiological surveillance system of addictions, 1994-2006

OBJETIVO: Determinar la relación que existe entre el consumo y número de sustancias y la presentación del suicidio. MATERIAL Y MÉTODOS: Los datos se tomaronde la cédula forense del Sistema de Vigilancia Epidemiológica de las Adicciones entre 1994 y 2006 de 27 entidades federativas participantes en México. RESULTADOS: El suicidio se presentó en 8.7% de las defunciones por causa violenta en el periodo de estudio. En los hombres se observó que a medida que aumentaba el número de sustancias se elevaba la posibilidad para fallecer por suicidio, en comparación con los decesos por otras causas (una sustancia: RM= 1.8; dos o más: RM= 3.3). En las mujeres, dicha posibilidad se mantiene prácticamente igual en relación con el aumento del número de sustancias detectadas (una sustancia: RM= 3.2; dos o más: RM= 3.6). CONCLUSIÓN: El consumo de sustancias es un factor importante vinculado con el suicidio en los sujetos cuya causa de defunción fue dictaminada por el Servicio Médico Forense mexicano.

OBJECTIVE: To determine the association between substance use and the number of substances with the presentation of suicide. MATERIAL AND METHODS: Data were taken from the forensic certificate of the Epidemiological Surveillance System of Addictions in the period between 1994 and 2006 from 27 states in Mexico. RESULTS: Suicide was detected in 8.7% of the violent deaths during the study period. Among men, it was observed that the increased number of substances increased the possibility for death by suicide, compared to deaths from other causes (one substance: OR = 1.8; two or more: OR = 3.3). In women, that possibility remains virtually unchanged with the increase in the number of substances detected (one substance: OR = 3.2; two or more: OR = 3.6). DISCUSSION: The use of substances is a major factor associated with suicide in the population whose cause of death was issued by the Mexican Forensic Medical Services.

Cuando falle la media, utilice un M-estimador / When the mean fails, use an M-estimator

En el campo de las adicciones en muchas ocasiones se tiene que trabajar con variables cuantitativas, siendo la media aritmética el índice de localización utilizado mayoritariamente. No obstante, el uso de este índice debería limitarse a aquellas situaciones en las que las distribuciones de las variables sean simétricas. El objetivo de este trabajo es ejemplificar la importancia de recurrir a estadísticos descriptivos adecuados para resumir variables cuantitativas, mediante el estudio de la cantidad de consumo de sustancias adictivas en la adolescencia. La muestra está formada por 9300 estudiantes con edades entre los 14 y los 18 años (47.1% chicos y 52.9% chicas) que contestaron de forma anónima un cuestionario sobre consumo de sustancias. Se describe la cantidad de consumo semanal de diferentes sustancias mediante índices de localización clásicos y pertenecientes al Análisis Exploratorio de Datos (EDA). Se puede observar cómo los resultados varían notablemente en función del estadístico elegido, siendo el M-estimador de Huber un índice con valores más "reales". La media aritmética no es un buen índice para acercarnos debidamente a la realidad del consumo de drogas cuando las distribuciones son asimétricas, siendo necesario utilizar índices resistentes, tal como, entre otros, el M-estimador de Huber (AU)

In the field of addictions on many occasions one has to work with quantitative variables, and the arithmetic mean is the most used location index. Nevertheless, the use of this index should be limited to those situations in which the distributions of the variables are symmetrical. The aim of this work is to exemplify the importance of recurring to adequate descriptive statistics in order to summarize quantitative variables, through the study of the quantity of consumption of addictive substances in adolescence. The sample is made up of 9300 students between 14 and 18 years (47.1% boys and 52.9% girls) who anonymously answered a questionnaire on consumption of substances. The quantity of weekly consumption of different substances is described using classical location indexes belonging to Exploratory Data Analysis (EDA). It can be seen how the results vary noticeably according to the statistics selected, with the Huber M-estimator as the index giving more "real" values. The arithmetic mean is not a good index in order to duly approach the reality of drug consumption when the distributions are asymmetrical, in which cases it becomes necessary to use resistant indexes such as, among others, Huber’s M-estimator (AU)

A pilot study of alcohol and drug-related traffic accidents and death in two Jamaican parishes, 1991

This study is a preliminary effort to document the role of drugs in motor vehicle accidents as it examines the presence of alcohol, marijuana and cocaine in blood samples of thirty-one motor vehicle fatalities. The study identified that males (90.3 percent) and pedestrians (41.9 percent) were killed most often. Evidence of alcohol intake was found in 77.5 percent of the fatalities and 35.5 percent had alcohol levels above the legal acceptable limits. Traces of marijuana were found in 22.5 percent and a combination of alcohol and marijuana in 22.5 percent of the victims (AU)

A pilot study of alcohol and drug-related traffic accidents and death in two Jamaican parishes, 1991

This study is a preliminary effort to document the role of drugs in motor vehicle accidents as it examines the presence of alcohol, marijuana and cocaine in blood samples of thirty-one motor vehicle fatalities. The study identified that males (90.3 percent) and pedestrians (41.9 percent) were killed most often. Evidence of alcohol intake was found in 77.5 percent of the fatalities and 35.5 percent had alcohol levels above the legal acceptable limits. Traces of marijuana were found in 22.5 percent and a combination of alcohol and marijuana in 22.5 percent of the victims