Journal of analytical toxicology最新文献

{"title":"SIGNIFY™ ER tricyclic antidepressant false positives in diphenhydramine overdose cases.","authors":"Noriko Nishimura, Sayaka Nagasawa, Go Inokuchi, Fumiko Chiba, Yumi Hoshioka, Naoki Saito, Maiko Yoshida, Shigeki Tsuneya, Yoshikazu Yamagishi, Hirotaro Iwase","doi":"10.1093/jat/bkaf077","DOIUrl":"https://doi.org/10.1093/jat/bkaf077","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitation of alcohols and acetone in postmortem blood and urine using headspace gas chromatography mass spectrometry.","authors":"Monika Edstam, Gustav Sundqvist, Robert Kronstrand","doi":"10.1093/jat/bkaf076","DOIUrl":"https://doi.org/10.1093/jat/bkaf076","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xylazine and major urinary metabolites detected in patients positive for fentanyl and xylazine.","authors":"Yanchun Lin, Bridgit O Crews","doi":"10.1093/jat/bkaf078","DOIUrl":"https://doi.org/10.1093/jat/bkaf078","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Acute and Chronic Pharmacokinetics and Pharmacodynamics of Oral Cannabidiol (CBD) With and Without Low Doses of Delta-9-Tetrahydrocannabinol (Δ9-THC).","authors":"David Wolinsky, C Austin Zamarripa, Tory R Spindle, McKenna Klausner, Edward J Cone, Ruth E Winecker, Svante Vikingsson, Ronald R Flegel, Eugene D Hayes, Lisa S Davis, David Kuntz, Marcel Bonn-Miller, George E Bigelow, Ryan Vandrey","doi":"10.1093/jat/bkaf075","DOIUrl":"https://doi.org/10.1093/jat/bkaf075","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etonitazepyne in counterfeit oxycodone tablets-a fatal case report.","authors":"Lena J Skarshaug, Live Midttun, Hege-Merete Krabseth, Per Ole Mobråten Gundersen, Miriam Hansen, Marianne Birgitte Brekke, Joachim Frost","doi":"10.1093/jat/bkaf065","DOIUrl":"https://doi.org/10.1093/jat/bkaf065","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOFT President's Letter.","authors":"Chris Heartsill","doi":"10.1093/jat/bkaf074","DOIUrl":"https://doi.org/10.1093/jat/bkaf074","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Trends in the Analysis of GHB in Hair.","authors":"Collin Kustera, Marc LeBeau, Sunil Sharma, Luis Arroyo","doi":"10.1093/jat/bkaf069","DOIUrl":"https://doi.org/10.1093/jat/bkaf069","url":null,"abstract":"<p><p>Hair analysis is a valuable tool in forensic toxicology, providing extended detection windows and critical insights into drug testing, usage trends, and drug-facilitated crimes. This systematic review was conducted using Scopus, Web of Science, and PubMed databases from March 2017 to September 2024, and evaluated 19 studies (16 research articles and 3 case reports) on the detection of γ-hydroxybutyrate (GHB) in hair. This review examines recent studies on GHB concentrations in hair, focusing on both endogenous and exogenous concentrations resulting from illicit and prescribed use, as well as the analytical methods employed. This review includes decontamination parameters, extraction techniques, and sample sizes used during the analytical method. New studies report that endogenous GHB levels range from 0.2 to 5.5 ng/mg, while exogenous levels vary widely from 0.3 to 239.6 ng/mg. Additionally, published results indicate that the frequency of use may be more significant than the dosage for exogenous GHB to be incorporated into the hair. A novel adjacent segmentation method has been proposed to differentiate endogenous from exogenous GHB, identifying local peaks within adjacent hair segments. Research into GHB-glucuronide as a biomarker has found it unreliable due to inconsistent correlations with exogenous use. Further research is needed to refine the interpretation of GHB levels in forensic applications.SSSSS.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence (AI) in New Psychoactive Substances (NPS) analysis: state-of-art and future perspectives.","authors":"Alessandro Di Giorgi, Simona Pichini, Francesco Paolo Busardò, Giuseppe Basile","doi":"10.1093/jat/bkaf071","DOIUrl":"https://doi.org/10.1093/jat/bkaf071","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chlorthalidone In Vitro Metabolite Identification for Documenting Exposure in Doping.","authors":"Alessandro Di Giorgi, Gloria Daziani, Anastasio Tini, Livio Tronconi, Jeremy Carlier, Omayema Taoussi","doi":"10.1093/jat/bkaf072","DOIUrl":"https://doi.org/10.1093/jat/bkaf072","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supporting evidence for 5-acetamido-N-desethylmetonitazene as a potential metabolite rather than a degradation product.","authors":"Rebecca Wood, Robert Moore","doi":"10.1093/jat/bkaf070","DOIUrl":"https://doi.org/10.1093/jat/bkaf070","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}