Journal of analytical toxicology最新文献

{"title":"Analysis of propranolol and its metabolites in postmortem human solid tissues and body fluids: LC-MS/MS approach with the standard addition method applied to a forensic case.","authors":"Mengchao Wang, Xiaoyu Zhou, Xiaolong Zhang, Yuxuan Chen, Jiajun Sun, Yaqin Sun, Jinlei Liu, Jie Gu, Wurita Amin, Koutaro Hasegawa","doi":"10.1093/jat/bkaf107","DOIUrl":"10.1093/jat/bkaf107","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop a highly sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of propranolol and its metabolites in human biological samples. By analyzing their presence in urine, postmortem biological fluids, and various solid tissues, the study could be of reliable forensic toxicological use for investigations in propranolol poisoning cases. In this study, the Standard Addition Method (SAM) was used for quantification, and its validation was mixed with one of the analyte's concentrations.</p><p><strong>Methods: </strong>A 0.1 mL aliquot of each body fluid sample or 0.1 g each of homogenized solid tissue was mixed with one of the analyte concentration standards, extracted with methanol, spiked with an internal standard (IS) using the SAM, and purified using magnesium sulfate and sodium sulfate. Following centrifugation and filtration, samples were analyzed via LC-MS/MS. Samples underwent enzymatic hydrolysis to quantify total metabolite concentrations (free plus conjugated) prior to analysis.</p><p><strong>Results: </strong>Phase I metabolites (propranolol, 4-hydroxypropranolol, propranolol glycol, N-desisopropylpropranolol, 1-naphthylenyloxyacetic acid, and 1-naphthol) and phase II metabolites (sulfate and glucuronide conjugates) were identified in urine. Among postmortem samples, propranolol was highest in the bile, followed by the lung tissue. Naphthoxylactic acid could be consistently detected in all samples except for the brain, suggesting its potential as a good biomarker for propranolol exposure.</p><p><strong>Conclusion: </strong>A validated LC-MS/MS method for determining propranolol and its metabolites in forensic samples was established, and it could also be applied to the authentic human samples obtained from a propranolol poisoning case. The findings could offer substantial and reliable support for investigating propranolol-related fatalities and contribute to the comprehensive understanding of the metabolism of propranolol in the human body.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794068","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":"Letter to the editor concerning the article: Aknouche F, Magny R, Maruejouls C, Trebuchet C, Fargeot K, Thion L, Valancony C, Scherrer F, Oussedik ND, Kintz P, Labat L, Houzé, P. (2025) Systemic organophosphate poisoning in child following anti-lice lotion application. Journal of Analytical Toxicology, bkaf096.","authors":"Artemisia Dona","doi":"10.1093/jat/bkaf112","DOIUrl":"10.1093/jat/bkaf112","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911947","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":"Evaluating solriamfetol interference in urine amphetamine immunoassays: a four-platform comparison.","authors":"Gopal Kumar, Mahesheema Ali","doi":"10.1093/jat/bkaf104","DOIUrl":"10.1093/jat/bkaf104","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827762","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":"Applications of machine learning for the general unknown screening of HRMS data within forensic toxicology.","authors":"Samantha Swan, Maria Sarkisian, Daniel Pasin, Luke N Rodda","doi":"10.1093/jat/bkaf109","DOIUrl":"10.1093/jat/bkaf109","url":null,"abstract":"<p><p>This review is intended for forensic toxicologists and cheminformaticians seeking an understanding of the past implementations and future directions of artificial intelligence (AI) and machine learning (ML) for high-resolution mass spectrometry (HRMS) data interrogation in forensic toxicology. It provides a comprehensive overview of the data processing steps required to generate valid ML inputs, including molecular representation, augmentation, tokenization, embedding, and spectral deconvolution. We examine the advantages and disadvantages of different modeling strategies and summarize existing models from forensic toxicology and related domains. Applications are grouped into spectra-to-compound, compound-to-spectra, and classification models, with attention to recent advances and the practical challenges of limited data, polysubstance use, and validation. By leveraging advances from related fields, ML can enhance forensic HRMS workflows, enabling more efficient unknown screening, structural elucidation, and classification of emerging substances. This review aims to bridge disciplinary perspectives and support the practical integration of ML into routine forensic toxicology.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843740","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":"N-pyrrolidino isotonitazene and its metabolites in post-mortem casework.","authors":"Rebecca Wood, Robert Moore","doi":"10.1093/jat/bkag027","DOIUrl":"https://doi.org/10.1093/jat/bkag027","url":null,"abstract":"<p><p>N-pyrrolidino isotonitazene (Isotonitazepyne) is an extremely potent novel synthetic opioid which has been detected internationally in counterfeit pharmaceutical tablets. Published data from post-mortem cases is extremely limited and no metabolite profiles from authentic case work have been published. This paper describes a number of post-mortem cases in which N-pyrrolidino isotonitazene was thought to play a significant role in the cause of death, as well as describing the detected metabolite profiles. Concentration ranges for N-pyrrolidino isotonitazene was reported to be 1.1-55.9 µg/L across the 4 cases. The presumptive metabolite 5-amino-N-pyrrolidino isotonitazene was also identified in all samples; n-pyrrolidino-4-hydroxy nitazene was present in 3 of the 4 urine samples; and N-pyrrolidino hydroxy isotonitazene was present in 1 sample. This study highlights some of the challenges associated with nitazene interpretation, such as the very wide concentration ranges encountered in potentially fatal cases, as well as providing provisional metabolite data which may aid in detecting future cases.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771960","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":"An Enduring Threat: NPS Benzodiazepines in Forensic and Clinical Toxicology from 2021-2025.","authors":"Kayla N Ellefsen, Erin L Karschner, Sandrine A M Mérette, Amy L Patton, Elisa N Shoff, Christina R Smith, Michael T Truver, Dani C Mata, Donna M Papsun","doi":"10.1093/jat/bkag026","DOIUrl":"https://doi.org/10.1093/jat/bkag026","url":null,"abstract":"<p><p>The proliferation and sustained detection of novel psychoactive benzodiazepines in forensic and clinical toxicology, combined with their potential for adverse events, poses an enduring threat to public health and safety with complex characteristics and challenges unique from other subclasses of novel psychoactive substances (NPS). This study aimed to systematically review the published effects, observations, and toxicological data from postmortem and human performance studies (including clinical, driving under the influence of drugs (DUID), and drug-facilitated crimes (DFC)) involving NPS benzodiazepines from 2021 to 2025. The challenges this class of compounds present to clinicians, toxicologists, and medical professionals were also addressed, including both analytical and interpretative challenges. Literature reviews were performed in PubMed, Google Scholar, Google Search, toxicology journals, and conference abstract proceedings using search terms such as \"NPS benzodiazepines,\" \"designer benzodiazepines,\" and compound specific searches; authoritative websites such as NPS Discovery, National Forensic Laboratory Information System, and the European Union Drug Agency were also consulted. A total of 259 NPS benzodiazepine-related studies were identified including 29 postmortem, 15 DUID, 27 clinical, and 5 DFC studies detailed in this review. NPS benzodiazepines were widely pervasive in both postmortem and human performance cases with overlapping toxic and recreational concentrations; often involving polysubstance use with other central nervous system depressants and stimulants. Unique clinical presentations, observed effects, and autopsy findings were also reported for NPS benzodiazepines. This review provides an updated, consolidated resource to support toxicologists and clinicians in interpretation, emerging risk assessment, and evolving challenges associated with NPS benzodiazepines across postmortem and human performance settings.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772041","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":"Analysis of seven selected cannabinoids in human plasma highlighting matrix and solution stability assessments.","authors":"David J Anderson, Tia S Freeman, Kalii S Caldwell, Logan R Hoggard, Christopher A Reilly, Joseph E Rower","doi":"10.1093/jat/bkaf087","DOIUrl":"10.1093/jat/bkaf087","url":null,"abstract":"<p><p>Cannabis consumption has and continues to increase dramatically, as does its legalization for recreational and/or medicinal use at the state, but not at the federal level. The increased consumption and legalization have spurred significant cannabis focused research, with particular interest in defining the pharmacokinetic characteristics of this complex natural product. Supporting this research requires a bioanalytical method that accurately and simultaneously quantifies the primary cannabinoids and their metabolites. The objective of this method validation was to meet pre-specified sensitivity targets (0.5 ng/mL for most analytes) from a low sample volume (0.2 mL) and a single extraction approach that could quantify Δ9-tetrahydrocannabinol, cannabidiol, and their metabolites. Moreover, we sought to rigorously characterize the stability of included cannabinoid analytes, both in solution and plasma. The developed assay required optimization of extraction and mobile phase solvents, as well as mass transitions to achieve the selectivity required to meet the desired sensitivity targets. Stability experiments indicated solution stability of no more than 6 months when stored in polypropylene at -30 or -80°C and ∼3 years (34.5 months) of plasma stability when stored in polypropylene at -80°C. The assay was successfully applied to ∼1650 samples without a batch failure. This validated LC-MS/MS assay provides unique information on cannabinoid stability and has been utilized to generate novel data on the pharmacokinetics of cannabis constituents and their metabolites.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in-depth study on Z/E-methoxime isomers in gas chromatography-quadrupole mass spectrometry analysis of C6-keto-opioids in human urine as their methoxime- and acyl-derivatives.","authors":"Kailyn M Shoffler, David A Barajas, Michael R Tomedi, Christopher L Hall, Gregory D Reynolds, Hieu T Dinh, Marisol S Castaneto, Pucheng Ke","doi":"10.1093/jat/bkaf090","DOIUrl":"10.1093/jat/bkaf090","url":null,"abstract":"<p><p>C6-keto-opioids, such as hydrocodone, hydromorphone, oxycodone, and oxymorphone, are a group of semi-synthetic morphine-like analgesics with extensive applications in clinical settings and high potential for abuse and misuse. Therefore, they have become targets of workplace forensic urine drug testing for years. Due to the undesired C6-C7 keto-enol tautomerization, the C6 ketone often needs to be deactivated prior to further derivatization for GC-MS analysis. Although it has been over two decades since the method of converting the C6 ketone to its methoxime-derivative was initially reported, little information has been published regarding the resulting Z/E-methoxime-derivative isomers' formation mechanism, stereo-configurations, or relative kinetic or thermodynamic features. Mixed Z/E-methoxime-derivative isomers create a potential peak resolution issue for GC-MS-based C6-keto-opioids identification and quantification, since the two isomers are often difficult to be completely separated by GC and they share common fragmentation pathways. We here provided the first detailed report and qualitative conformational analyses of the Z/E-methoxime-derivative isomers of C6-keto-opioids and their isomerization under the non-aqueous Brønsted-Lowry acidic conditions. By in-depth studying the C6-keto-opioids Z/E-methoxime-derivative isomers, we were able to gain important insights into potential reaction condition optimization with an attempt to reduce the formation of the minor methoxime-derivative isomer, thus, to minimize the potential interferences caused by co-existing of the two isomers and further improve the method's limit of detection and/or limit of quantification. Our report offered valuable information that could facilitate other laboratories using the similar derivatization procedures for GS-MS-based C6-keto-oipoids testing to improve their testing method sensitivity and enhance their analysis product quality.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274724","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":"In silico metabolite prediction and LC-HRMS confirmation for forensic analysis of a fatal case involving novel synthetic opioid N, N-dimethyl etonitazene.","authors":"Miao Zhang, Jialin Feng, Hang Chen, Ping Xiang, Hui Yan, Junbo Zhao","doi":"10.1093/jat/bkaf099","DOIUrl":"10.1093/jat/bkaf099","url":null,"abstract":"<p><p>Nitazenes are a class of new psychoactive substances (NPS) belonging to the synthetic opioids. It has potent μ-opioid receptor agonist activity. In this study, we investigated an authentic forensic human blood and urine sample from an individual that died from the use of N, N-dimethyl etonitazene. To enable rapid analysis in authentic forensic sample, a method was developed utilizing in silico metabolite prediction and liquid chromatography high-resolution mass spectrometry (LC-HRMS) for blood and urine samples.In this study, LC-HRMS was used to analyze authentic blood and urine samples, and Sygma software was used to predict metabolites. Based on the predicted results, targeted analysis methods of LC-HRMS data were used to study the metabolites of blood and urine. N, N-dimethyl etonitazene and seven metabolites were identified in blood and urine samples. Among them, there were four phase I metabolites, which respectively correspond to four metabolic pathways: N-demethylation (M1), 5-amination (M2), 4'-hydroxylation (M4), N-oxidation (M6). There were three phase II metabolites corresponding to two metabolic pathways, respectively: acetylation (M3), glucuronidation (M5, M7). M1, M2, and M3 were identified in blood sample, and all metabolites were identified in urine sample. In this study, Sygma software was used to predict metabolites, and LC-HRMS method was employed to specifically analyze the metabolites of N, N-dimethyl etonitazene in authentic forensic human samples. The time required for data analysis was significantly reduced through in silico metabolite prediction. We recommend the 5-amination metabolite (M2) as a potential biomarker in blood and urine samples of N, N-dimethyl etonitazene. In addition, this study filled the gap in the study of N, N-dimethyl etonitazene metabolism. It also provided real data supplementation for the metabolism of nitazene analogues. The prediction of metabolites by using Sygma provided a certain reference for the future application of artificial intelligence in the field of forensic analysis.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400804","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":"Evaluation of screening results of an untargeted metabolite-based LC-MS/MS screening for vitreous humor.","authors":"Johanna L Becher, Maxima Kummer, Frank T Peters, Dirk K Wissenbach","doi":"10.1093/jat/bkaf091","DOIUrl":"10.1093/jat/bkaf091","url":null,"abstract":"<p><p>In case of standard biological postmortem matrices such as blood or urine being unavailable, vitreous humor (VH) has been shown to be a versatile matrix used as an alternative for postmortem systematic toxicological analysis for the detection of drugs and their metabolites. This study focused on the qualitative detection of drugs in VH using an untargeted metabolite-based LC-M/MS screening approach. VH samples were retrospectively analyzed by LC-MS/MS after being worked-up by protein precipitation. In n = 96 samples, 418 detections were recorded. Those corresponded to 121 different xenobiotics. Cardiovascular drugs being the most frequently detected drug class followed by (local) anesthetics, neuroleptics, and antidepressants. Drug exposure was indicated 227 times (∼ 54%) solely by the presence of the parent compound. One hundred thirty-seven times (∼ 32%) a parent compound and corresponding metabolite(s) were detected. Fifty-four times (∼ 13%) a drug exposure was indicated solely by the detection of metabolites. Out of those 54 detections, 32 times corresponding metabolites were not common commercially available. Therefore, the authors suggest that metabolite information should be considered for a VH-based screening approach. Screening for metabolites will lead to ∼13% more detections, if the corresponding metabolites are covered by the applied screening approach. The obtained results pointed out that some compounds are exclusively found in form of their corresponding phase II metabolites. No linkage between protein binding or molecular weight was found for the detection of a compound in VH either by parent compound or metabolite(s).</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307807","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}