Journal of analytical toxicology最新文献

The emergence of new psychoactive substances (NPS) and the number of new chemically diverse substances in the global illicit drug market have significantly increased over the last few years. Designer benzodiazepines are some of the most misused NPS worldwide, contributing to both nonfatal and fatal drug overdose cases. The use of desalkylgidazepam and bromazolam has recently emerged, and their prevalence has been internationally reported. In this study, we quantified desalkylgidazepam and bromazolam using gas chromatography coupled with mass spectrometry (GC-MS) in the postmortem specimens of a subject found deceased due to suspected drug overdose. A 24-year-old white male with a history of drug use was found unresponsive and not breathing in his home with drug paraphernalia nearby. A yellow powdery substance and prescription tablets were also found at the scene. The GC-MS analysis of the postmortem blood and urine samples confirmed the presence of fentanyl, desalkylgidazepam, and bromazolam. The desalkylgidazepam concentration was 1100 ng/mL in the blood, which was higher than previous reports in the literature, and estimated to be 89 ng/mL in the urine. The bromazolam concentration was 352 ng/mL in the blood and estimated to be 398 ng/mL in the urine. Additionally, fentanyl was detected in the blood (11 ng/mL), and fentanyl, norfentanyl, and gabapentin were detected in the urine. The present study aims to provide the toxicological community with information regarding a fit-for-purpose analysis of two NPS benzodiazepines.

Liquid chromatography-triple quadrupole mass spectrometry (LC-MS-MS) assays are frequently utilized for screening and confirmatory purposes in the forensic toxicology laboratory. While these techniques are excellent for the targeted identification and quantitation of a wide variety of drug classes, validation and determining fit-for-purpose is a significant requirement for each method. In the USA, the American National Standards Institute and Academy Standards Board first edition of Standard 036 currently serves as a primary resource in forensic toxicology method validation and mandates that laboratories evaluate critical performance characteristics to help ensure the production of forensically defensible results. Due to the variability of specimen quality frequently encountered in the discipline of postmortem toxicology, the State of Maryland Office of the Chief Medical Examiner Forensic Toxicology Laboratory routinely analyzes solid tissue specimens as part of the medicolegal death investigation process and evaluates liver as a representative solid tissue matrix during method validation. Authentic postmortem specimens (e.g. liver, kidney, skeletal muscle, and spleen) were used to investigate the effects of analyzing solid tissue homogenate versus solid tissue supernatant on bias, precision, and ionization suppression/enhancement of Δ9-THC and Δ9-THCCOOH. Bias was <20% for Δ9-THC and Δ9-THCCOOH in liver homogenate and supernatant with a single exception of the low QC concentration for Δ9-THC in liver homogenate (-29%). Within-run and between-run CV was <20% for Δ9-THC and Δ9-THCCOOH in liver homogenate and supernatant. Δ9-THC and Δ9-THC-d3 exhibited significant ion suppression in both liver homogenate and supernatant, while Δ9-THCCOOH and Δ9-THCCOOH-d3 showed both ion suppression and enhancement in these matrices. Noticeable quantitative differences were observed in authentic postmortem solid tissue homogenate and supernatant specimens despite evaluating identical tissue samplings. A brief discussion of the results is presented using a validated LC-MS-MS method for the confirmation and quantitation of Δ9-THC and Δ9-THCCOOH in postmortem casework.

Clonazolam is a designer triazolobenzodiazepine first synthesized in 1971 and is primarily used for its anxiolytic and sedative effects. It became a drug of misuse in 2012 and is known for its high potency and long duration of effect. Previous studies of nitrobenzodiazepines, such as nitrazepam, clonazepam, and flunitrazepam, as well as their metabolites, have demonstrated that bacterial species native to the gastrointestinal tract and active during postmortem (PM) decomposition are capable of affecting positivity and compound-to-metabolite ratios. Further studies have not been performed with clonazolam; however, it possesses the nitro functional group necessary for this biotransformation. To understand whether clonazolam may be similarly affected, PM cases (n = 288) and driving under the influence of drugs (DUID, n = 54) cases, positive for 8-aminoclonazolam reported by NMS Laboratories from 2020 to 2023, were selected for inclusion in this study. Concentrations of clonazolam and 8-aminoclonazolam were evaluated, and concurrent identification of parent drugs and their metabolites occurred less frequently in PM cases (n = 1, 0.30% of cases) than in DUID cases (n = 21, 38% of cases). The clonazolam concentration in one PM case was 13 ng/mL. In DUID cases, the median clonazolam concentration was 4.0 ng/mL and ranged from 2.0 to 10 ng/mL. 8-Aminoclonazolam had median concentrations of 13 and 19 ng/mL, with ranges 2.0-580 and 2.8-59 ng/mL for PM and DUID cases, respectively. Due to the ever-changing landscape of the designer benzodiazepine market, in vitro studies of PM microbial biotransformation of clonazolam are unavailable. The data reported herein provide valuable information in the absence of such studies and represent an alternative method of investigating this phenomenon as a potential cause of parent nitrobenzodiazepine to metabolite conversion.

Caffeine is a naturally occurring stimulant present in dozens of plant species including Coffea arabica and Camellia sinensis, from which we obtain coffee and tea, respectively. It is one of the world's most widely consumed psychoactive substances frequently used to increase alertness, elevate mood, and ward off fatigue. In traditional preparations, caffeine is generally well-tolerated by the consumer. However, complications can arise with the addition of caffeine to products like energy drinks, medications, and supplements. Furthermore, with pure caffeine accessible online, a consumer may unknowingly or inadvertently consume caffeine in dangerous amounts. Symptoms of caffeine toxicity include classic central nervous system stimulation side effects, such as agitation, insomnia, gastrointestinal distress, tachycardia, seizures, and death in extreme cases. To evaluate concentrations of toxicological significance, caffeine cases were assessed at a large reference laboratory (NMS Labs). From 2019 to 2023, 406 blood cases underwent confirmation testing via LC-MS-MS; the mean and median caffeine concentrations were 35 and 4.8 µg/mL, respectively. While most caffeine-containing cases indicate traditional use in the general population with concentrations <25 µg/mL (62%, N = 254), 10% (N = 42) of the cases were >100 µg/mL, indicating levels which may contribute to a fatal outcome. To gain insight into the significance of caffeine in determining the cause and manner of death, cases with various manners of death are presented. Despite being one of the most common toxicological findings in medicolegal death investigations, caffeine is often overlooked. Screening results should undergo scrutiny, and confirmation testing should be considered in cases where caffeine intoxication is prominently featured in the case history or scene investigation.

Synthetic cannabinoids emerged in the early 21st century and have continued to evolve and flourish to present day. Like other novel psychoactive substances (NPS), synthetic cannabinoids have been sold under the guise of legitimate products. Some examples include "potpourri," "incense," and herbal material. Between May 2020 and December 2023, the United States Army Criminal Investigation Laboratory, Drug Chemistry Division (USACIL) received 29 seized drug cases mentioning "blue lotus" or "valerian root." In 90% of these cases, at least one exhibit contained one or more synthetic cannabinoids. During the same timeframe, the Armed Forces Medical Examiner System, Division of Forensic Toxicology received 65 toxicology cases that contained synthetic cannabinoids and/or their corresponding metabolites where case history mentioned "blue lotus." The most frequently observed synthetic cannabinoids between laboratories were 5F-MDMB-PICA, ADB-BUTINACA, and MDMB-4en-PINACA. Innocuous branding and marketing may deceive law enforcement, investigators, and healthcare providers into believing that the adverse effects of erratic behavior, sedation, slurred speech, and hallucinations are a result of toxicity from botanical extracts (e.g. apomorphine and nuciferine in blue lotus). Due to the dangerous nature of these NPS, synthetic cannabinoid screening is recommended for all cases where there is suspected use of vaping products suggested to contain "blue lotus" or "valerian root" as vendors continue to conceal the presence of these compounds.

Postmortem toxicology is an ever-changing landscape presenting challenges for toxicologists and medical examiners. Trends can vary for certain benzodiazepines. While diazepam use tends to remain constant, alprazolam and clonazepam ebb and flow depending on prescription trends and street popularity. Novel benzodiazepines like etizolam vary in casework depending on legal restrictions and black market availability. In May 2022, the first case of the designer benzodiazepine, bromazolam, was detected in Jefferson County Coroner/Medical Examiner's Office casework. Between then and December 2023, an additional nine cases have been observed. Bromazolam is the brominated analog of the low-dose benzodiazepine, alprazolam, and is likely similar in potency. As bromazolam is a potent benzodiazepine, low concentrations of this novel drug are likely to contribute to central nervous system depression in opioid overdose cases. We present 10 cases in which bromazolam was detected in postmortem samples at the University of Alabama at Birmingham toxicology laboratory. The decedents ranged in age from 20 to 41 years. Most of the decedents were White (n = 8; 80%) and male (n = 7; 70%). Bromazolam concentrations ranged from 21 to 3220 ng/mL (mean 401 ng/mL). All but one case were polydrug, and all deaths were related to drug toxicity. Fentanyl was detected in 8 of the 10 decedents, with concentrations ranging from <2.5 to 97 ng/mL (mean 30 ng/mL). Additional drugs detected were methamphetamine, ethanol, oxycodone, methadone, cocaine, amphetamine, morphine, and diphenhydramine. While all manners of death were ruled as accidental, bromazolam was included in the cause of death statements in 9 of the 10 cases. Capturing important emerging drug trends in the death certificate is critical to help inform public health and medical colleagues for preventive measures and treatment in the continued drug epidemic.

Over the last 20 years, there has been a significant increase in fentanyl-related deaths in Ontario, Canada. This report examines toxicological findings in a series of death investigations in which fentanyl was quantitated to identify the prevalence, trends, and demographic data associated with fentanyl in Ontario, Canada, and to highlight the changes in these trends since fentanyl began appearing in casework in Ontario in the early 2000s. A retrospective study of all cases in which fentanyl was quantitated in blood, using liquid chromatography (LC)-tandem mass spectrometry (MS-MS), was conducted for the time period between 1 January 2020 and 31 December 2022. A total of 4395 cases were included; 77% of the decedents were male, and 23% was female with ages ranging from 0 to 95 years. The most frequently classified cause of death was mixed drug toxicity (69%) followed by fentanyl intoxication at 19%. Less than 10% of cases where fentanyl was quantitated were classified as nondrug-related deaths. Fentanyl concentrations in all cases ranged from 1.3 to >2000 ng/mL. Other drugs were frequently detected with fentanyl. In mixed drug toxicity cases, stimulants were the most frequently encountered class of drugs: cocaine was identified in 51.8%, and methamphetamine was observed in 43.0% of cases. Detailed reports for select cases were included to provide additional insight into the different case types and to show the difficulty in interpreting blood concentrations without additional detailed case histories. This study provides valuable information for the scientific and medical community regarding the continued use of fentanyl and how patterns of fentanyl use have evolved since it began to appear in forensic casework.

The US Food and Drug Administration's (FDA) regulatory oversight over electronic cigarettes (e-cigs) includes access restriction for persons <21 years of age and flavor restrictions for "cartridge-based" products. Despite the restrictions, consumption by US youth perseveres. Studies on youth e-cig use are limited by the reliability and accuracy of self-reports. As an alternative to self-reports, the current study examined nicotine, cannabinoid, and unlabeled e-cigs and other vaping products confiscated from Virginia public schools to characterize trends among students. Findings highlight a shift from JUUL and pod-based products to single use disposable e-cigs following the FDA flavor restrictions on cartridge-based e-cigs. Chemical analysis of e-liquids by gas chromatography-mass spectrometry identified a wide variety of flavorants and an increase in the prevalence of synthetic coolants. Most confiscated products were nicotine salt formulations, but the prevalence of cannabinoid-based vaping products increased. The popularity of flavored disposable e-cigs highlights the need for further restrictions to reduce youth consumption. The increasing use of synthetic coolants instead of menthol may suggest that manufacturers are employing tactics to bypass regulations. Continued youth access to e-cigs and the abundance of cannabinoid-based products is problematic from health and safety perspectives. Continued research incorporating confiscated product analysis can be used to understand youth access to vaping products and evolutions in manufacturing practices.

Occasionally, obtaining an adequate or acceptable postmortem blood specimen for drug analysis is not possible due to factors such as decomposition, exsanguination, or embalming. Submandibular salivary gland tissue, one of three major types of salivary gland tissue in the oral cavity of humans, has been reported to be a viable alternative postmortem specimen for toxicological testing. In this study, we evaluated the performance of the Randox Evidence Investigator instrument and Randox DOA (Drugs of Abuse) Ultra Whole Blood Array for the semi-quantitative determination of 21 immunoassays in an alternative matrix, submandibular salivary gland tissue. We analyzed 132 submandibular salivary gland tissue specimens and compared the generated results to concomitantly collected postmortem whole blood specimen results. Oxycodone 2, meprobamate, barbiturate, benzodiazepine assay 1, zolpidem, and buprenorphine all showed perfect agreement (Cohen's kappa score = 1.00) between the submandibular salivary gland tissue results and the postmortem whole blood results; dextromethorphan, fentanyl, benzoylecgonine, methamphetamine, tricyclic antidepressants, oxycodone 1, and opiate showed an almost perfect agreement (Cohen's kappa score = 0.81-0.99); methadone, generic opioids, and amphetamine exhibited substantial agreement (Cohen's kappa score = 0.61-0.80). Tramadol demonstrated fair agreement (Cohen's kappa score = 0.41-0.60). The lowest measure of agreement was observed with cannabinoids, meeting criteria for slight agreement (Cohen's kappa score = 0.01-0.20). An application of the techniques described in this study could be implemented in postmortem toxicology laboratories as well as medical examiners offices to provide preliminary drugs of abuse test results that can be used to direct additional testing. This study highlights the successful integration of a novel specimen matrix and an "off-label" use of an established analytical technique.

Diphenhydramine has been available for decades in non-prescription formulations for the treatment of allergic reactions, insomnia and symptomology associated with colds. In addition, dimenhydrinate, a precursor to diphenhydramine, is available in preparations for the treatment of nausea and vomiting. Diphenhydramine and other first-generation antihistamines are being replaced by second- and third-generation antihistamines which are associated with fewer side effects, notably the lack of drowsiness; however, there are still a variety of therapeutic uses that have persisted in both adults and children. In this study, postmortem blood concentrations of diphenhydramine were determined, by liquid chromatography tandem mass spectrometry, in seven children with concentrations ranging from 0.051 to 2.6 mg/L. The cause of death in two cases was attributed, at least in part, to diphenhydramine toxicity while diphenhydramine detection in five cases was considered incidental to the cause of death.