Journal of analytical toxicology最新文献

{"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}

{"title":"Case-control study of mitragynine deaths in Florida.","authors":"Christian M Iuteri, Ryan J Sawyers, Connor M Byrne, Max Trojano, Josef Thundiyil","doi":"10.1093/jat/bkag017","DOIUrl":"10.1093/jat/bkag017","url":null,"abstract":"<p><p>Kratom use has increased in the USA, with its primary alkaloid, mitragynine, detected in postmortem toxicology, and implicated in reported fatalities. This study evaluated toxicologic concentrations and autopsy findings associated with deaths attributed to mitragynine. Autopsy and postmortem toxicology reports were obtained from the majority of Florida medical examiner districts over 5 years for decedents in whom mitragynine was listed as a cause of death (mitragynine-induced fatalities). A comparison group included cases from a single county in which mitragynine was detected but not deemed causal (mitragynine-associated deaths). Demographic, toxicologic, and autopsy data were abstracted using standardized instruments. Thirty-eight mitragynine-induced fatalities and 111 mitragynine-associated deaths were identified, with similar demographic characteristics between groups. Mitragynine-associated deaths all featured co-exposures, including fentanyl (n = 84), cocaine (n = 49), and ethanol (n = 29). Mitragynine-induced fatalities had no toxic levels of any other substance and demonstrated higher rates of pulmonary edema (55.6% vs 31.5%), hepatomegaly (47.4% vs 14.4%), minor facial trauma (18.4% vs 5.4%), and cardiomegaly (47.4% vs 11.8%). Mean blood mitragynine concentrations were substantially higher in mitragynine-induced fatalities (2486 µg/L; 95% CI 1607-2863) compared with mitragynine-associated deaths (179 µg/L; 95% CI 217-375), suggesting a concentration-dependent association with fatal toxicity. Mitragynine toxicity accounts for a notable number of deaths.</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":"147468078","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":"Simultaneous analysis of Δ9-THC, Δ8-THC, CBD, and CBN in breath aerosols collected using cannabix technologies breath collection unit.","authors":"Shaza Deeb, Zaire E Fabian, Mikko Määttä, Pedro Fraccarolli, David A Engelhart","doi":"10.1093/jat/bkag016","DOIUrl":"10.1093/jat/bkag016","url":null,"abstract":"<p><p>A simple, accurate, and cost-effective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method has been developed and validated for the simultaneous quantification of Δ9-tetrahydrocannabinol (Δ9-THC), Δ8-tetrahydrocannabinol (Δ8-THC), cannabidiol (CBD), and cannabinol (CBN) in breath aerosols collected using the Cannabix Technologies' Breath Collection Unit (BCU). The method is suitable for use in workplace drug testing and in the investigation of driving under the influence of drugs (DUID) cases. The method was validated according to ANSI/ASB Standard 036, First Edition 2019 guidelines. A lower limit of quantification (LLOQ) of 2.5 pg/L was achieved. Calibration curves were linear (R2 > 0.995) and quality control (QC) accuracy between 91.3% and 100.5% with precision (%CV) less than 17.7%. No major matrix effects or drug interferences were observed. Samples were stable at room temperature and refrigerated at 2-8°C up to 7 days. Breath samples were collected using the BCU from volunteer regular cannabis users before cannabis consumption and at multiple timepoints after smoking cannabis up to 90 minutes. The results verified the methods ability to capture and quantitate the cannabinoids in breath. The data indicated similar concentration versus time trends for THC metabolism assessed from breath to that previously reported from blood. Breath is an alternative, non-invasive sample matrix that holds promise for identifying recent cannabis use.</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/PMC13218819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271116","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":"Evaluating the impact of fentanyl immunoassay cutoff concentrations in emergency department, maternal, and neonatal populations.","authors":"Maxwell L Harsha, Kathryn Weaver, William A Clarke, Ashley R Rackow","doi":"10.1093/jat/bkag025","DOIUrl":"10.1093/jat/bkag025","url":null,"abstract":"<p><p>Qualitative urine drug screens (UDSs) are essential in clinical toxicology for assessments of drug exposure and are commonly employed by emergency departments to provide rapid results that inform care. Fentanyl, a potent synthetic opioid, is of significant public health concern due to rising overdose rates. However, fentanyl is also administered clinically as an analgesic, which may result in positive UDS assessments for patients with iatrogenic exposure. Positive UDS findings may cause patient anxiety, provider confusion, and lead to medicolegal concerns in clinical settings such as labor and delivery and neonatology. As such, it is essential that UDSs are utilized appropriately and that the positivity threshold for the assay is rigorously evaluated to serve the clinical need. This study examined UDS utilization within a quaternary care system over a 1-year period. A subset of remnant urine specimens from UDSs was further analyzed using high resolution mass spectrometry (HRMS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to focus on the impact of fentanyl immunoassay cutoff concentrations in high-volume populations. At our institution, the adult emergency department (ED) had the highest number of specimens ordered (5901), while neonatal units had the least (727). Notably, fentanyl positivity rates were the highest in neonatal units at 34%. Quantitative analysis of remnant urine samples from the ED, labor and delivery (L&D), and neonatal units showed higher fentanyl concentrations in the ED, indicative of illicit use, and lower concentrations in L&D and neonates, consistent with analgesic administration. Raising the immunoassay cutoff from 1.0 to 5.0 ng/ml would convert iatrogenic positives to negatives while retaining illicit positives. These findings underscore the need to evaluate UDS cutoff values for improved clinical performance in different populations.</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":"147716779","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":"Sample validity lessons learned from challenging cases and proposed biomarkers for synthetic urine detection.","authors":"Samantha Joubert, Catherine Lynch, Andrew Carter","doi":"10.1093/jat/bkag022","DOIUrl":"10.1093/jat/bkag022","url":null,"abstract":"<p><p>Toxicology laboratories rely on a combination of on-site and laboratory based validity testing to detect dilution, adulteration, and substitution in urine samples collected for drugs of abuse testing. At Melbourne Pathology, Sample Validity Testing (SVT) includes on-site checks such as temperature, creatinine, color, and supervised collection, as well as routine laboratory testing of all specimens for creatinine, pH, and oxidants. Additional validity testing is performed when a specimen is deemed suspicious, including osmolality and the biomarkers urea, uric acid, amylase, and γ-glutamyltransferase (GGT). We describe three cases in which SVT was critical in identifying inauthentic specimens, and one where SVT resulted in the inaccurate identification of an authentic case as inauthentic due to a medical condition. We also present the SVT results from seven synthetic urine (SU) samples detected in routine casework. Urea and uric acid proved somewhat successful at identifying SU, present in three of the SU samples. GGT and amylase proved the most effective at identifying SU, with none of the SU samples containing the enzymes. These biomarker assays were rapid, cost‑effective, and readily implemented using existing biochemistry workflows. Our findings highlight that no single validity measure is sufficient in isolation; instead, results should be interpreted collectively and on a case‑by‑case basis. As SU formulations continue to evolve, laboratories may benefit from adopting additional, non‑routine validity tests tailored to their operational capacity.</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":"147529100","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":"Comparative performance of methadone urine immunoassays based on real-world data reveals assay interference.","authors":"Jayson V Pagaduan","doi":"10.1093/jat/bkag023","DOIUrl":"10.1093/jat/bkag023","url":null,"abstract":"<p><p>Urine drug screen (UDS) immunoassays remain essential tools in clinical toxicology due to their rapid turnaround time and operational efficiency. However, their susceptibility to cross-reactivity continues to pose challenges, particularly in complex patient populations receiving multiple medications. Verification studies performed prior to assay implementation often rely on limited sample sets and may not fully capture real-world assay performance. Ongoing post-implementation monitoring, especially through comparison with confirmatory assays such as liquid chromatography-tandem mass spectrometry (LC-MS/MS), is therefore critical for identifying unexpected assay behavior and maintaining analytical reliability. This study evaluated the real-world concordance of two methadone immunoassays-the Architect MULTIGENT Methadone assay and the Roche Methadone II (MDN2) assay-with an in-house LC-MS/MS method capable of detecting methadone and its primary metabolite, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP), at a cutoff concentration of 100 ng/mL. A total of 6753 Architect and 6255 Roche methadone screening results were retrospectively reviewed. The Architect assay demonstrated a 2.8% positivity rate, with 94.8% of positive screens confirmed by LC-MS/MS, corresponding to a 5.2% false-positive rate. In contrast, the Roche assay produced a higher positivity rate of 3.6% but a substantially lower confirmation rate of 69.8%, yielding a 30.2% false-positive rate (χ2 = 106, P < .05). Medication review of Roche false-positive cases revealed frequent use of quetiapine and vortioxetine, consistent with previously reported cross-reactivity. Additional medications historically associated with methadone immunoassay interference were also identified. These findings highlight significant performance differences between two widely used methadone immunoassays and underscore the importance of continuous, data-driven post-implementation surveillance. Confirmatory testing data such as LC-MS/MS results, can reveal clinically meaningful assay limitations, support accurate interpretation of unexpected results, and ultimately improve the reliability of UDS testing in diverse patient populations.</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":"147673580","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":"Confirmatory gas chromatography-mass spectrometry drug testing in pediatric patients: a clinical case series highlighting false-positive results and child protection implications.","authors":"Nicolás Fernández, Patricia Noemí Quiroga","doi":"10.1093/jat/bkag020","DOIUrl":"10.1093/jat/bkag020","url":null,"abstract":"<p><p>Drug exposure in pediatric patients represents a major clinical and forensic challenge, particularly when initial urine drug screening relies on immunoassays with limited specificity. False-positive and false-negative results may lead to inappropriate clinical decisions or delayed child protection interventions. We conducted a retrospective case series of 14 pediatric patients (0-5 years) with suspected drug exposure evaluated in a hospital emergency setting. Positive immunoassay urine drug screens were submitted for confirmatory analysis using gas chromatography-mass spectrometry (GC-MS) at a reference toxicology laboratory. GC-MS confirmation identified a wide range of illicit and prescription substances and metabolites, including benzoylecgonine, cocaine, ecgonine methyl ester, phenobarbital, para-hydroxy-phenobarbital, lorazepam, morphine, sertraline and its metabolites, hydroxymidazolam, MDMA, MDA, and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH). In several cases, GC-MS resolved discordant screening results by identifying immunoassay false positives caused by cross-reactivity or by detecting substances missed during initial screening. Confirmatory GC-MS testing directly influenced clinical management and supported child protection decisions in cases of suspected neglect, accidental ingestion, or environmental exposure. These findings reinforce the critical role of mass spectrometry-based confirmation in pediatric toxicology to ensure diagnostic accuracy and appropriate clinical and legal outcomes.</p>","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":"147628085","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":"Micro-QuEChERS extraction method optimization for quantification of designer benzodiazepines in forensic postmortem blood samples.","authors":"Karla Aparecida de Oliveira Souza, Janaína Aparecida Reis Teodoro, Débora Zorron Berlinck, Ana Paula Knak Rezendes, Daniela Mendes Louzada de Paula, Fabricio Souza Pelição, Elvis Medeiros de Aquino, Victor Alexandre Percinio Gianvecchio, Mauricio Yonamine, Jose Luiz Costa","doi":"10.1093/jat/bkag008","DOIUrl":"10.1093/jat/bkag008","url":null,"abstract":"<p><p>The aim of this study was to develop and validate a quantitative method for the analysis of designer benzodiazepines in postmortem blood samples using micro-QuEChERS extraction and liquid chromatography tandem mass spectrometry (LC-MS/MS). A comprehensive optimization of the method was performed using a multivariate statistical approach, incorporating validation criteria in line with established practices for method validation in forensic toxicology. The method showed linearity between 1 and 200 ng/mL (r2 > 0.990), with good imprecision (<9.8%) and inaccuracy (<11.1%) evaluated at three different quality control concentrations. Matrix effects and recovery rates were found to be better than 58% and 77.5%, respectively. No carryover or interferences were detected during the analysis. The method was effectively utilized on two real forensic postmortem blood samples, both of which tested positive for bromazolam, showing concentrations of 31 and 40 ng/mL. The micro-QuEChERS extraction method demonstrated satisfactory analytical performance and is an environmentally sustainable option, minimizing the use of solvents and reagents, with potential for application in both clinical and forensic analyses, aligning with green analytical toxicology principles.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131974","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}