Journal of analytical toxicology最新文献

In 2004, the National Safety Council's Alcohol, Drugs, and Impairment Division set out to provide guidance for the standardization of laboratory testing practices in driving under the influence of drugs and fatal motor vehicle crash investigations after identifying a lack of consistency in testing practices in this type of casework. A survey about laboratory testing practices, scopes of testing, and cutoffs was created using SurveyMonkey®, an online survey instrument, and sent to laboratories throughout the USA and Canada. Based on the analysis of survey results and discussion, the first set of recommendations was published in 2007 with recommended scope and cutoffs for drug screening and confirmation in blood and urine. Subsequent surveys were sent to laboratories in 2012, 2016, and 2020, followed by updates to the recommendations published in 2013, 2017, and 2021. This publication highlights the 2024 survey results in addition to trends in drug testing practices and drug use positivity. With each survey year, data exhibited a shift of laboratories using newer and more sensitive technology such as liquid chromatography-high-resolution mass spectrometry for screening and confirmation. Overall, data show that laboratories are willing to implement changes to be in compliance with the recommendations; however, challenges with instrument capacity and technology, lack of staffing, training, laboratory space constraints, and time associated with method development and validation hinder compliance with all of the recommendations. While compliance increased, 51% of laboratories reported using the practice of stop-limit testing, an administrative decision to stop testing if a blood alcohol concentration result is at or above a certain concentration, which further hinders the understanding of the drug-impaired driving problem. Delta-9-Tetrahydrocannabinol and/or metabolites remained the most prevalent drug reported by laboratories, followed by stimulants.

Guanfacine, a medication used to treat attention deficit hyperactivity disorder (ADHD), activates alpha-2A adrenergic receptors in the brain to reduce symptoms. However, its central alpha-2 agonist activity can cause adverse events, such as somnolence, bradycardia, and hypotension. We present the case of a 6-year-old boy (15 kg) with no history of regular medication use who was admitted to the hospital with unexplained prolonged somnolence and bradycardia. Initial evaluation ruled out common causes; however, ingestion of his mother's prescription medication was suspected. Liquid chromatography-quadrupole time-of-flight mass spectrometry confirmed the presence of 6 ng/mL of guanfacine in his serum, which, together with his symptoms, led to a diagnosis of guanfacine intoxication. To our knowledge, this is the first report of guanfacine intoxication in a young child without ADHD with documented serum concentration measurements. This case may help in the recognition and diagnosis of guanfacine toxicity in pediatric patients.

Cannabinoid use and misuse has been rising since 2011, and the development of new cannabinoid derivatives, partially due to the passage of the Farm Bill in 2018, and more relaxed legislation, has complicated testing for this drug class. The impact on child welfare in homes with cannabis substance use remains a concern, so detection of environmental exposure to cannabinoids is hugely beneficial. This article reports a validated confirmation method which detects delta 9-tetrahydrocannbinol (Δ9-THC), delta 8-tetrahydrocannbinol (Δ8-THC), delta 10-tetrahydrocannbinol (Δ10-THC) and cannabidiol (CBD) in environmentally exposed hair specimens via liquid chromatography tandem mass spectrometry (LC-MS-MS) following a supported liquid extraction. From February 2024-October 2024, 30.5% (n = 1787) of specimens tested positive for at least one analyte. The most common analyte was Δ9-THC (26.8%, n = 1574), followed by Δ8-THC (9.0%, n = 528), CBD (6.1%, n = 359) and Δ10-THC (0.4%, n = 24). While most of the specimens contained multiple analytes, it was found that 21.4% of the positive specimens had a single analyte exposure: 1062 specimens only confirmed for Δ9-THC, 165 specimens only confirmed for Δ8-THC, and 28 specimens only confirmed CBD. The addition of Δ8-THC, Δ10-THC, and CBD to the cannabinoids assay improved the detection of cannabinoids related cases, increasing our total positivity rate by an additional 3.6% (n = 213). The detection of all these analytes is crucial for reliable and accurate detection of cannabinoid environmental exposure.

The SIGNIFY™ ER test for diphenhydramine (DPH) overdose yields false-positive results for tricyclic antidepressants (TCA) in multiple cases, complicating the identification of the causative substance of poisoning. We investigated the causes of TCA false positives in DPH overdose cases. From March 2021 to September 2023, 11 cases of DPH overdose with no concomitant TCA use were identified and categorized into two groups: four with false-positive TCA results (FPG) and seven with negative results (NG) in SIGNIFY™ ER. The blood and urinary DPH concentrations and the urinary concentrations of its three major metabolites (diphenhydramine N-oxide, DPH-NO; N-desmethyl diphenhydramine, DM-DPH; and diphenhydramine N-glucuronide, DPHG) were measured using liquid chromatography quadrupole time-of-flight mass spectrometry, and differences between the groups were examined. Standard substances of DPH, DPH-NO, DM-DPH, DPHG, and mixtures of DPH-NO and DPHG at ratios of 50:50, 25:75, and 75:25 were added to blank urine samples, and TCA was measured using the SIGNIFY™ ER. The concentrations of the substances in the FPG and NG, respectively, were: blood DPH, 0.9-9 and 0.33-49 µg/mL; urinary DPH, 10-110 and 2.3-36 µg/mL; urinary DPH-NO, 110-170 and 0.05-10 µg/mL; urinary DM-DPH, 5.3-47 and 0.13-3.4 µg/mL; and urinary DPHG, 28-370 and 0.24-67 µg/mL. When using spiked urine samples, false positives were obtained for DPH, DPH-NO, DM-DPH, and DPHG at 500, 110, 200, and 70 µg/mL, respectively. In the mixtures of DPH-NO and DPHG, false positives were obtained at all three ratios. TCA false positives in the SIGNIFY™ ER test for DPH overdose cases are suggested to be yielded by DPH-NO and DPHG. For a positive test result without information on TCA use, DPH overdose should be considered.

Traditionally, ethanol and related compounds have been analyzed by headspace gas chromatography with flame ionization detection. However, this does not provide structural information, relying solely on retention time for identification. With a mass spectrometry (MS) detector, isotope labeled internal standards can be used, eliminating the risk associated with using internal standards like 1-propanol, that can be present in postmortem samples. Furthermore, the use of ion ratios for confirmation of identity eliminates the need for dual injections on columns with different selectivity. In addition, the MS detector provides the ability to include a full scan which could be helpful in the identification of other volatile unknowns. This prompted the implementation of a headspace gas chromatographic-mass spectrometric method quantifying methanol, ethanol, 2-propanol, 1-propanol, 1-butanol, and acetone while enabling the qualitative detection of a number of other volatiles. A 100 µl sample aliquot was dispensed into a 20 mL headspace vial together with 1000 µL of internal standard solution. Samples were analyzed using an Agilent 7697A headspace sampler coupled to an Agilent Intuvo 9000 gas chromatograph and an Agilent 5977 mass spectrometer. The developed method was successfully validated and compared to current methodology before being implemented into routine analysis. The introduction of quantitative determination of putrefactive alcohols enables prospective studies of the possible relationship between the formation of ethanol and 1-propanol and 1-butanol and increased the diagnostic power of the method. The simultaneous detection of other volatiles important in postmortem toxicology in all cases increased the scope of routine analysis and the use of mass spectrometry improved the identification of analytes.

Xylazine in an anesthetic drug used for the sedation of animals that is increasingly appearing as an adulterant in uncontrolled drug supplies, primarily illicit fentanyl. The ability to detect xylazine exposure by urine drug testing may improve monitoring of this drug trend and our understanding of the effects and risks associated with xylazine exposure. Currently, limited information is available regarding the elimination of xylazine or its metabolites in humans. In this study we report quantification of xylazine and 4-hydroxy-xylazine (4-OH-x) in hydrolyzed urine specimens collected from 109 patients testing positive for fentanyl and xylazine using liquid chromatography tandem mass spectrometry (LC-MS/MS). 4-OH-x was a minor urinary metabolite in most patients with a median metabolite-to-xylazine (MR) concentration ratio 0.09. Additional urinary metabolites were identified including oxo-xylazine (oxo-x), OH-oxo-xylazine (OH-oxo-x), OH-sulfone-xylazine (OH-sulfone-x), and sulfone-xylazine (sulfone-x), with median MR peak area ratios of < 0.01, 0.60, 0.30, and 1.60, respectively. Sulfone-x signal exceeded that of xylazine in more than 70% of urine specimens. Sulfone-x is not glucuronidated and does not appear to form positional isomers. Additional studies are needed to examine whether detection of xylazine metabolites may improve the sensitivity and/or extend the detection time window for xylazine exposure.

Introduction: Hemp products (cannabis with ≤0.3% Δ9-tetrahydrocannabinol (Δ9-THC)) are federally legal, but few controlled experiments have explored drug test results, pharmacokinetics, or pharmacodynamics.

Methods: Healthy adults (n = 60) self-administered 1.5 mL medium-chain triglyceride (MCT) oil containing 100 mg cannabidiol (CBD) and either 0 mg, 0.5 mg, 1 mg, 2 mg, 2.8 mg or 3.7 mg Δ9-THC (n = 10 per group). The study included an 8-hour acute dose laboratory session (Phase 1), a 14-day outpatient drug exposure period with twice daily dosing (Phase 2) and a 7-day washout period (Phase 3). Measures including urine, blood, subjective drug effects, and cognitive and psychomotor performance were assessed repeatedly throughout the experiment.

Results: At least one participant receiving Δ9-THC doses of 1.0 mg or greater had at least 1 positive urine drug test (Δ9-THC-COOH immunoassay screen ≥50ng/mL and LC-MS/MS confirmation ≥15ng/mL) during Phase 1 and the number of positive urine samples increased with Δ9-THC dose. Positive urine drug tests were observed during the Phase 2 outpatient drug exposure period from at least one participant in each dose condition that contained any amount of Δ9-THC. One urine specimen in the CBD only dose condition tested positive during Phase 2. Two positive urine samples were observed after the 1-week washout (Day 21). Blood concentrations of Δ9-THC were very low in all dose conditions, and there were no significant differences between the CBD only dose group and Δ9-THC-containing dose groups on any pharmacodynamic outcome.

Conclusions: Individuals subject to drug testing should recognize that hemp products contain detectable amounts of Δ9-THC. Conventional drug testing cannot reliably distinguish between illicit cannabis and legal hemp-derived product use, and a positive urine Δ9-THC test may result from low doses that do not produce intoxication or impairment.

Benzimidazole opioids (nitazenes) are novel synthetic opioid receptor agonists that over the last few years have emerged on recreational drug markets, and their abuse has become a concern worldwide. In particular, limited documentation of their pharmacology and toxicology, along with their unpredictable presence in counterfeit medicines mistaken for established brands, pose significant challenges. Herein, we present a case of fatal intoxication with the nitazene etonitazepyne, after intake of tablets appearing like, and thus mistaken as, oxycodone. The assertion of etonitazepyne's implication in the case was delayed by several months, due to lack of information about and access to seized tablets. Eventually, an analytical method using liquid chromatography coupled to a Waters Xevo TQ-S tandem quadrupole mass spectrometer (LC-MSMS) was developed and documented. Using this method, etonitazepyne was confirmed in the tablets and quantified at a concentration of 0.32 ng/mL in both femoral blood and vitreous fluid sampled at autopsy of the deceased. The femoral blood concentration is in the lower range compared to previously published etonitazepyne-related deaths. This case illustrates the challenges with detecting nitazenes and the imminent health risk counterfeit products poses, even for experienced drug users.

Analytical toxicology is a discipline of forensic toxicology which applies analytical techniques for the determination of drugs of abuse in biological and non-biological matrices. To this concern, artificial intelligence (AI), particularly machine learning (ML), is innovating analytical toxicology by improving data processing and facilitating the identification of New Psychoactive Substances (NPS). The aim of this review was to explore the current application of AI in this field and to highlight the future perspectives. A literature search was performed in several scientific databases to review articles reporting the implementation of AI models for analytical toxicological purposes. The most frequent applications of these technologies were for compound identification, molecular structure prediction and retention time prediction. AI proved to be a valuable tool for analytical toxicologists for the capability to process large amount of data which are typically obtained by untargeted approaches.

Diuretics are commonly used in doping because they can conceal the presence of performance-enhancing substances in an athlete's urine through dilution and promote rapid weight loss. As a result, these substances are prohibited in sports by the World Anti-Doping Agency (WADA) under the S5 category ("Diuretics and Masking Agents"). Chlorthalidone, a thiazide-like diuretic, is medically used as an antihypertensive agent and is prescribed for conditions such as heart failure and liver cirrhosis. However, it is also misused in doping. The detection of chlorthalidone or its metabolite markers in an athlete's urine is essential to prove consumption. Therefore, the aim of the study was to assess the metabolism of the substance in humans. For this purpose, chlorthalidone metabolites were predicted with GLORYx (Hamburg University, Germany) to identify the transformations that may occur with higher probability; the compound was incubated with 10-donor-pooled human hepatocytes to simulate hepatic metabolism; and the incubates were analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) and software-aided data mining. In silico simulations predicted 11 Phase II metabolites, with N-acetylation at the sulfonamide group being the predominant transformation (88% probability score); other major reactions included O-glucuronidation, O-sulfation, and glutathione conjugation, with probability scores lower than 70%. Two metabolites were identified in in vitro hepatocyte incubates and presented a reduction or a hydroxylation at the phthalimidine moiety. To the best of the authors' knowledge, these metabolites are specific to chlorthalidone and can be targeted as markers for analytical screening in anti-doping controls.