Journal of analytical toxicology最新文献

{"title":"N-pyrrolidino isotonitazene and its metabolites in post-mortem casework.","authors":"Rebecca Wood, Robert Moore","doi":"10.1093/jat/bkag027","DOIUrl":"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":"2026-06-04","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":"Determination of nitazenes in postmortem casework and their prevalence in the State of Maryland.","authors":"Michael Fagiola, Rebecca Phipps","doi":"10.1093/jat/bkag031","DOIUrl":"10.1093/jat/bkag031","url":null,"abstract":"<p><p>The 2-benzylbenzimidazole class of synthetic opioids-more commonly referred to as the \"nitazenes\"-are the latest of several classes of novel psychoactive substances to predominate the illicit drug market. Following the class-wide scheduling of fentanyl analogs and fentanyl-related substances in 2018, forensic toxicology laboratories in the United States began to see a proliferation of these novel synthetic opioids in casework initially stemming from the emergence of isotonitazene in 2019. Nitazenes are structurally distinct from fentanyl but share similar pharmacologic and toxicologic activity as mu-opioid receptor agonists with varying degrees of potency. In this study, we report the emergence and subsequent prevalence of the nitazenes in postmortem casework in the State of Maryland between May 2024 and August 2025. Analysis was completed utilizing a mixed-mode cationic exchange solid-phase extraction protocol and detection by ultra-performance liquid chromatography-triple quadrupole mass spectrometry. Four hundred and thirty postmortem cases were analyzed, with 3% of cases positive for one or more nitazenes. The most prevalent nitazenes detected were metonitazene (62% of positive cases), N-desethyl protonitazene (31% of positive cases), and N-pyrrolidino protonitazene (31% of positive cases). Only one case involved nitazenes as the sole substance of toxicologic significance; in all other cases, they were never the only drug detected and were frequently co-detected alongside fentanyl (85% of cases), followed by quinine (77% of cases), despropionyl fentanyl (69% of cases), cocaine/benzoylecgonine (62% of cases), and para-fluorofentanyl (54% of cases). Given the ever-changing landscape of novel psychoactive substances, the potency and increasing prevalence of these synthetic opioids raise significant concerns and underscore the need for ongoing surveillance, advancements in analytical techniques, and targeted public health interventions to mitigate their impact on mortality trends.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054637","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":"Drugs in formalin-fixed specimens - a review on reactivity and stability.","authors":"Julius Hoffmann, Fabian Picht, Carolin Richter, Karen Blümke-Anbau, Valentin Cepus","doi":"10.1093/jat/bkag043","DOIUrl":"10.1093/jat/bkag043","url":null,"abstract":"<p><p>Formalin-fixed specimens represent particular challenges in the field of forensic toxicology. Despite being a rare occurrence, the circumstances of certain cases may require toxicological analyses of embalmed or fixed tissues. However, the preservation causes a variety of physical and chemical processes influencing the concentration and the detectability of many target analytes. While redistribution of drugs between tissue and formaldehyde solution may be reflected in measuring both tissue and fixing solution concentrations, reactions of target analytes with formaldehyde may lead to more complex behavior of drugs. Some of those degradation pathways have been comprehensively described, e.g. Eschweiler-Clarke conversion of amines. Considering both the redistribution and reactions of drugs in fixed specimens, most toxicologically relevant substances can be detected, either directly or by identifying specific degradation products. This review summarizes the current knowledge of drug-formaldehyde reactions and documents the stability of a broad variety of drugs.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211291","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":"Differentiation of 2-, 3-, and 4-fluorofuranylfentanyl using high performance liquid chromatography-mass spectrometry and human liver microsomes.","authors":"Takaharu Iwaki, Yasuhisa Oida, Miku Morikawa, Kousuke Itoh, Kosei Iwai, Konosuke Abe, Erina Kohyama, Tetsuro Ito, Hiroyuki Tanaka, Tsuyoshi Yokoi, Kiyoyuki Kitaichi","doi":"10.1093/jat/bkag056","DOIUrl":"10.1093/jat/bkag056","url":null,"abstract":"<p><p>The structural similarity of positional isomers of fentanyl analogs makes their forensic differentiation difficult, particularly when the parent compounds exhibit similar chromatographic behavior and product-ion spectra. This study evaluated the differentiation of 2-, 3-, and 4-fluorofuranylfentanyl (2-, 3-, and 4-FFF) using high-performance liquid chromatography-mass spectrometry (HPLC-MS) and human liver microsomes (HLMs). The synthesized positional isomers were analyzed using gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and HPLC-ion trap-time-of-flight mass spectrometry (HPLC-IT-TOF-MS). Although the parent isomers were separated by GC-MS, their retention times and product-ion spectra obtained by HPLC-MS/MS were highly similar under the present conditions. Incubation with HLMs supplemented with NADPH, UDPGA, and alamethicin produced three Phase I metabolic categories: an oxidative N-dealkylated metabolite of FFF (M1), monohydroxylated FFF metabolites (M2a and M2b), and an amide hydrolysis product of FFF (M3). Glucuronide conjugates were not detected under the present analytical conditions. Although M1 was the predominant metabolite, M1 did not retain the complete FFF structure. M2a and M2b were putatively assigned as monohydroxylated metabolites that retained the complete FFF structure, and may therefore support the differentiation of FFF positional isomers, although their retention times did not allow the differentiation. M3, which did not retain the complete FFF structure, showed distinct retention times among the three positional isomers, providing chromatographic information useful for metabolite-based differentiation. The in vitro elimination half-lives differed among 2-, 3-, and 4-FFF under the present HLM conditions, suggesting possible differences in the pharmacokinetic properties of these positional isomers. These findings indicate that HPLC-MS analysis using HLMs provides useful analytical information for differentiating FFF positional isomers.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351656","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":"A retrospective review of phencyclidine in hair samples of subjects from the United States workplace drug testing population.","authors":"G Neil Stowe, Elvan Loni, Alejandro Gonzalez, Ryo Furukawa, Ryan B Paulsen, Michael I Schaffer, Marvin Pietruszka","doi":"10.1093/jat/bkag029","DOIUrl":"10.1093/jat/bkag029","url":null,"abstract":"<p><p>The dissociative anesthetic phencyclidine (PCP) remains an encountered analyte in typical routine testing in forensic toxicology. Herein, we describe a validated GC/MS method for PCP measurement in subjects using human head and body hair with a limit of detection (LOD) of 100 pg PCP/mg hair, with method linearity established from 100 to 15 000 pg PCP/mg hair. The GC/MS method was used to analyze samples from the USA workplace drug testing population (n = 368 samples) containing PCP over the years 2021 to 2025. The statistical comparison of PCP median concentrations for samples reported as black or brown in color or samples collected using head or body hair found no significant median concentration difference in either case. Many of the samples (65%) had the concurrent presence of at least one additional drug other than PCP, with cocaine (50%), amphetamines (20%), and cannabinoids (18%) as the most commonly observed drug substances. With the exception of an increased median concentration in year 2021, annual PCP median hair concentrations over the time period of this manuscript were stable.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972664","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":"Development and application of a simplified, quantitative method for 30+ New Psychoactive Substances in hair.","authors":"Seokjin Hwang, Bruno Pereira Dos Santos, Ashef Ameer, Patricia de Souza Schwarz, Leticia Birk, Alberto Salomone, Sarah Eller, Tiago Franco de Oliveira, João Pedro Matias, Marta Concheiro-Guisán, Ana Miguel Fonseca Pego","doi":"10.1093/jat/bkag052","DOIUrl":"10.1093/jat/bkag052","url":null,"abstract":"<p><p>The rapid emergence of novel psychoactive substances (NPS) poses a significant challenge for forensic toxicology and public health. While blood and urine enable rapid detection for early warning systems, long-term monitoring is essential for retrospective exposure assessment and temporal trend analysis. In this context, hair represents a valuable biological matrix; however, multi-class NPS determination remains difficult due to their chemical diversity and typically low concentrations. In this work, we targeted 12 synthetic opioids, 8 synthetic cathinones, 3 dissociatives, 3 designer benzodiazepines, 3 hallucinogens, and 2 synthetic cannabinoids. Sample preparation included a three-step wash procedure (water, methanol, and ethyl acetate), followed by simultaneous pulverization and methanolic extraction of 20 mg of hair, using an Omni Ruptor bead-mill homogenizer (10 cycles, 40 s at 4.5 m/s with dwell periods; total time ∼43 min). After centrifugation (5000 rpm, 10 min), extracts were evaporated under nitrogen stream at 40°C (20 psi) and reconstituted in 100 µl of 90:10 (v/v) water/acetonitrile, both containing 0.1% formic acid, followed by filtration. Chromatographic separation was achieved by liquid chromatography on a Kinetex C18 column (100 × 2.1 mm, 1.7 µm) using gradient elution with a total runtime of 10 min. Identification and quantitation were performed by tandem mass spectrometry in positive electrospray ionization using multiple reaction monitoring with quantifier and qualifier transitions. The method was validated according to ANSI/ASB Standard 036. Linearity was demonstrated from 5 to 500 pg/mg. Intra- and inter-day precision were <20% and bias within ±20% for most analytes, with no significant carryover or interferences observed. Matrix effects were observed but consistent across analytes, allowing reliable quantitation. Application to authentic hair samples from electronic music festival attendees in Europe and Brazil confirmed the presence of emerging NPS. This integrated pulverization-extraction approach enables rapid, robust multi-class NPS detection in hair for biomonitoring and forensic applications.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258135","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":"Performance evaluation of a commercial LC-high-resolution-MS platform for untargeted whole blood analysis: comparison with immunoassay and LC-low-resolution-MS urine screening and targeted LC-MS/MS whole blood quantification.","authors":"Annina Bovens, Lana Brockbals, Thomas Kraemer, Andrea E Steuer","doi":"10.1093/jat/bkag050","DOIUrl":"10.1093/jat/bkag050","url":null,"abstract":"<p><p>In forensic toxicology (FT), drug of abuse (DoA) screening is essential yet challenging. This study presents a vendor-based, high-resolution (HR) LC-MS/MS blood screening method implemented without in‑house optimization, in comparison to immunoassay-based and low-resolution (LR) urine screening approaches simultaneous to (semi)quantification. The HR-method allows detection of more than 3000 analytes, including DoAs, drugs and suspected new psychoactive substances (NPS). Following protein precipitation, analytes qualitatively identified in 500 authentic whole-blood samples using the HR-method were qualitatively compared with results from the immunoassay and LR urine screening. Additionally, 82 common DoAs and drugs were (semi)quantitatively validated according to ANSI and GTFCh guidelines and quantitative performance was assessed against a fully validated targeted LC-MS/MS method (MRM mode). In total, the HR-method detected 819 (83%) of the 994 analytes identified by the LR urine screening. Substances not captured by the HR approach typically showed concentrations below the identification limit and/or were of negligible relevance in FT. The HR blood screening detected 66% of all cases positive for THC and/or its metabolites, whereas the LR urine screening failed to detect these compounds entirely. Incorporation of the HighResNPS® database enabled the tentative identification of 14 NPS. Seventy-four (90%) of the 82 DoAs demonstrated accuracy within ± 30%, precision (CV) ≤ 30% and quantitative results of 100 authentic cases were consistent with those from the targeted LC-MS/MS method which is generally considered the gold standard for quantification. Overall, the HR blood screening is superior to the LR urine screening for most analyte classes, enabling simultaneous detection of DoAs, their metabolites and NPS. The semi-quantitative validation of 74 drugs and the quantitative comparison confirmed the method's reliability in distinguishing between subtherapeutic, therapeutic and toxic concentrations without the need for drug class-specific optimization, thereby saving time, effort and costs. This untargeted approach combines screening with (semi)quantification while supporting routine workflows, research applications and retrospective analysis of new emerging substances.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264676","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":"Universal LC-MS/MS screening for GHB: advancing routine detection in postmortem toxicology and accuracy of death investigations.","authors":"Luke N Rodda","doi":"10.1093/jat/bkag021","DOIUrl":"10.1093/jat/bkag021","url":null,"abstract":"<p><p>Gamma-hydroxybutyric acid (GHB) is an endogenous compound and central nervous system depressant with legitimate therapeutic applications but frequent illicit use. Historically, GHB has been excluded from routine systematic toxicology testing because its detection typically required targeted analysis, limiting testing to cases where GHB use was specifically suspected. In 2020, our office implemented a validated LC-MS/MS screening platform that enabled GHB to be analyzed efficiently and universally across all forensic case types, including postmortem death investigations. Between May 2020 and April 2025, 15 GHB-associated fatalities were identified, with 11 (73%) having no investigative suspicion of GHB use. Most decedents were male, White, with the cohort having a median age of 39 years. Twelve deaths (80%) were accidental, and three (20%) were suicides. Concentrations in both blood and urine were consistent with exogenous exposure across all cases, frequently in the context of polysubstance stimulant use. Integration of GHB testing into routine testing workflows revealed multiple previously unrecognized fatalities, demonstrating that universal inclusion of GHB enhances accuracy in death certification, operational efficiency, and the completeness of forensic toxicology surveillance.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529081","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":"Determination of specific absorbance (A¦) for four designer benzodiazepines.","authors":"Bryan Shou-Chung Ku, Jay R Vargas","doi":"10.1093/jat/bkag019","DOIUrl":"10.1093/jat/bkag019","url":null,"abstract":"<p><p>Specific absorbance (A¦) is a unitless value defined as the absorbance of a 1% (w/v) solution measured at a 1 cm path length. Establishing reliable specific absorbance values allows forensic toxicology laboratories to verify the concentration of analytical stock solutions. Designer benzodiazepines have appeared with increasing frequency in forensic casework but often lack validated reference values. This study determined specific absorbance values for bromazolam, etizolam, flualprazolam, and flubromazepam using ultraviolet-visible spectroscopy in an aqueous acidic solution. Measurements were collected in duplicate at three concentrations across three days at the wavelength of maximum absorbance for each compound. Inter-run and intra-run variability were evaluated using the coefficient of variation, and the reliability of the values was classified according to Clarke's Analysis of Drugs and Poisons criteria. The experimentally derived values reported here provide reference information that may assist laboratories in verifying analytical standards for emerging benzodiazepines.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13211992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494034","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":"The detection of N-propionitrile orphine in a urine sample.","authors":"Rebecca Wood, Robert Moore, Donna Iula","doi":"10.1093/jat/bkag024","DOIUrl":"10.1093/jat/bkag024","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690158","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}