Journal of analytical toxicology最新文献

Novel benzodiazepine (NBz) detections in Victorian coronial cases started early in 2018 and have continued to increase in number and type up to December 2022. The eleven different NBz detections included etizolam (n=82), flualprazolam (n=43), clonazolam or 8-aminoclonazolam (n=30), bromazolam (n=15), clobromazolam (n=13), phenazepam (n=13), flubromazolam (n=12), flubromazepam (n=8), desalkylflurazepam (n=6), diclazepam (n=2), and estazolam (n=1). The pattern of detections varied over the 5-year period, with different compounds appearing over different time frames. The most recent NBz to appear were bromazolam, clobromazolam, flubromazepam and phenazepam; whereas etizolam had been seen regularly in case work since 2018. Of the total 133 deaths, 95 were considered drug related deaths by forensic pathologists with at least one additional CNS depressant also present capable of contributing to death. All deaths involved other (non-benzodiazepine) CNS active drugs, although many involved multiple NBz, with five or more different benzodiazepines detected in eight cases.

Accidental overdose cases continue to rise due to the opioid epidemic in the USA, namely, the widespread availability and use of fentanyl. Medical examiners and coroners across the country have been subsequently burdened, and with limited resources, some seek alternative triaging processes to identify overdoses. Point-of-care urine dipstick testing at autopsy is one such idea that may be used in various ways to instigate or negate the need for an autopsy or regular forensic toxicology laboratory testing. This study investigated the frequency and estimated quantitative fentanyl and norfentanyl concentrations in the postmortem urine of fentanyl-related accidental overdose deaths, as well as the effectiveness of commercially available point-of-care urine dipstick tests based on such concentrations. A total of 1550 fentanyl-related accidental overdose cases, where both the postmortem peripheral femoral blood and urine were tested, were reviewed. Of these, using sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) laboratory testing, 82 cases (5%) had a positive fentanyl or norfentanyl detection in the blood, while fentanyl or norfentanyl remained undetected in the urine. Furthermore, a comparison of commercially available urine dipstick test cut-offs and authentic casework with estimated urine concentrations revealed that at a fentanyl/norfentanyl cut-off level of 5 ng/mL, 19% of these fentanyl-related accidental overdoses would result in a false negative, 24% at 10 ng/mL, 25% at 20 ng/mL, 51% at 50 ng/mL, and 61% at 100 ng/mL. The study found that the use of urine dipstick tests, as a decision-maker for the initiation of further comprehensive routine toxicology laboratory testing, or to support cause and manner of death determination, leads to both false-positive and false-negative predictions in fentanyl accidental overdoses.

As cocaine is not only incorporated into hair via blood following ingestion but also by external contamination, hair samples are commonly tested for cocaine metabolites to prove ingestion. However, cocaine metabolites can also be present as degradation products in typical street cocaine samples. The present study investigates minor hydroxycocaine metabolites para- and meta-hydroxycocaine together with para- and meta-hydroxybenzoylecgonine in seized cocaine (n=200) and hair samples from routine casework (n=2,389). Analytical results of hair samples were interpreted using an established decision model for the differentiation between actual use and external contamination using metabolic ratios (metabolite to cocaine). They were further examined concerning background of request, hair color, body site of sample collection, sex, and metabolic ratios of the main metabolites (benzoylecgonine, norcocaine, and cocaethylene). All seized cocaine samples were positive for para- and meta-hydroxycocaine with a maximum percentage of 0.025 and 0.052 %, respectively; para- and meta-hydroxybenzoylecgonine were detected in 55 and 56 % of samples with a maximum percentage of 0.044 and 0.024 %, respectively. Analytical results of 424 hair samples (17.7 %) were interpreted as being predominantly from contamination; the majority of these samples were from traffic medicine cases (83.7 %). Metabolic ratios of minor hydroxycocaine metabolites were significantly higher in hair samples interpreted as originating from use than in samples interpreted as caused by contamination. Metabolic ratios for hydroxycocaines were significantly higher in forensic cases compared to abstinence controls and also in black hair compared to blond/gray hair. However, this was not the case for hydroxybenzoylecgonine metabolic ratios. No statistical difference was observed with regard to the donor's sex. Hydroxycocaine metabolic ratios increased significantly with increasing ratios of norcocaine and cocaethylene to cocaine, respectively. The study demonstrates that hydroxycocaine metabolites (including thresholds for their metabolic ratios) must be used for a reliable interpretation of positive cocaine results in hair samples.

N-ethylhexedrone (NEH) is a new cathinone derivative with, currently, low toxicokinetic and toxicodynamic knowledge. We present three documented clinical cases of NEH intoxication with plasma and urine concentrations. A thorough search for metabolites was performed. The three patients were admitted to the emergency department, and two out of the three were hospitalized for an extended period. While recovering from the drug effects, 12-24 h after nasal intake of New Psychoactive Substance (NPS), the patients described the following disorders: anxiety, feelings of persecution, asthenia, anhedonia, abulia, psychomotor slowing and loss of consciousness. NEH was identified in all samples by liquid chromatography-high resolution mass spectrometry (LC-HRMS), and quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). Quantitative analysis showed decreasing concentrations over time: for Case 1, from 97.2 (Day 1, D1) to 0.7 (Day 7, D7) µg/L for plasma, and from 724 (D1) to 0.5 (D7) µg/L for urine. NEH concentration of 7.9 µg/L was found in the plasma collected at admission for Case 2. For Case 3, concentrations ranging from 49 (D1) to 1.8 (D7) µg/L in plasma, and from 327.3 (Day 6, D6) to 116.8 (D7) µg/L in urine were found. NEH was no longer detected in the urine sample at Day 10. Elimination half-life was estimated at 19, and 28 hours in Patients 1 and 3, respectively. Four metabolites were identified in blood and urine: reduced NEH, dealkyl-NEH, reduced dealkyl-NEH and hydroxy-NEH. The cases presented highlight the long detectable lifetime of NEH. Characterization of the metabolites will allow better identification of the consumption of this drug. Serious adverse events can be observed after NEH consumption, as two out of the three patients required intubation and ventilation. A syndrome of inappropriate antidiuretic hormone secretion (SIADH) was also diagnosed. Two out of the three cases are notable because of the number of samples collected and because NEH was the only drug of abuse detected.

In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences (e.g., metabolic capabilities, body size, etc.) between the pediatric and adult populations. In particular, the administration of over-the-counter (OTC) medications needs careful consideration, as dosages given to the pediatric population (0 days-18 years), particularly those given to individuals <5 years of age, tend to be lower than those given to individuals closer to adulthood. Postmortem pediatric data from 11 years (2010-2020) was compiled. A total of 1413 positive cases contained one or more of the following common OTC medications: antihistamines (brompheniramine, chlorpheniramine, diphenhydramine, doxylamine and pheniramine), pain relievers (acetaminophen, naproxen, ibuprofen and salicylates), cold/flu medications (dextro/levomethorphan, guaifenesin, ephedrine and pseudoephedrine), gastrointestinal aids (dicyclomine and loperamide) and/or sleep aids (melatonin). Antihistamines, cold/flu medications and pain relievers are the most common classes of drugs encountered in the postmortem pediatric population. To evaluate trends, three main age groups were created: ≤5 years old (5 U, birth-5 years old), middle childhood (MC, 6-11 years old), and early adolescence (EA, 12-18 years old). When considering the data, it must be noted that many of these drugs may be co-administered in single and/or multi-drug formulations. In addition, some drugs may have a variety of uses, e.g. antihistamines may also be used as sleep aids. Of note, the prevalence of cases involving those aged 6-11 years old was far less than their younger and older pediatric counterparts. With the widespread availability of OTC medications, unintentional overdoses, recreational misuse and suicidal overdoses can occur in the vulnerable, pediatric population.

Xylazine has emerged in recent years as a dangerous adulterant in illicit fentanyl use, and methods for the detection of xylazine in toxicology panels are still lagging. We developed methods for the screening and quantitation of xylazine in oral fluid (OF), a popular testing medium due to its ease of collection and reflection of presence in blood for many classes of drugs. Enzyme-linked immunosorbent assays were employed for the rapid screening of xylazine directly from the collection device buffer with a cutoff of 1 ng/mL. Solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry facilitated the confirmation and quantification of xylazine as low as 0.1 ng/mL and a dynamic range of 0.1-25 ng/mL. Selectivity, ionization suppression, processed sample stability, and dilution effect were also assessed. The method was validated through the American National Standards Institute/American Academy of Forensic Sciences Standards Board (ANSI/ASB) Standard 036, first edition from 2019, and found to be accurate, precise, and robust. Living human subject OF samples collected within substance use disorder and therapeutic drug monitoring clinics received between September 2023 and January 2024, with the specific request to test for xylazine (n = 57), were screened. Presumptive positive samples were confirmed using the validated method. Xylazine confirmed living human subject OF sample concentrations ranged from 1.2 to 23.3 ng/mL.

Brain can be a useful specimen for toxicology testing as it is a protected and isolated organ with lower metabolic activity than other tissues, but there is currently no published data supporting the stability of stimulant drugs in prepared brain homogenates. Brain homogenates were evaluated to determine the stability of the following stimulant drugs: amphetamine, benzoylecgonine, bupropion, cocaethylene, cocaine, ephedrine, methylenedioxyamphetamine, methylenedioxymethamphetamine, methamphetamine, and phentermine. Four different homogenates were prepared at a 1:4 dilution with deionized water and fortified at 500 ng/mL of: cocaine without sodium fluoride, cocaine with 1% sodium fluoride, stimulant drugs other than cocaine without sodium fluoride, and stimulant drugs other than cocaine with 1% sodium fluoride. The fortified homogenates were aliquoted into 13 × 100-mm screw cap tubes and stored at room temperature (∼20°C), refrigerated (2-8°C), or frozen (<-5°C) and analyzed in triplicate on Days 0, 1, 3, 7, 14, 30, 60, and 90. Analytes were considered stable as long as the difference in analyte/internal standard response ratio from Day 0 was less than 20% and the peaks met qualitative acceptance criteria. All analytes were stable for up to 90 days when stored frozen with or without sodium fluoride and had variable stability at all other evaluated conditions.