Edmund Rab, Ellen Sellers, Marta-Sofia Lindo-Cardoso, Gabrielle Wall, Faizan Khan
{"title":"Simultaneous screening and quantitation of drugs and their metabolites in postmortem vitreous humor by liquid chromatography-high resolution mass spectrometry.","authors":"Edmund Rab, Ellen Sellers, Marta-Sofia Lindo-Cardoso, Gabrielle Wall, Faizan Khan","doi":"10.1093/jat/bkaf049","DOIUrl":"10.1093/jat/bkaf049","url":null,"abstract":"<p><p>Postmortem vitreous humor may be used for toxicological analysis if blood and urine are unavailable or where postmortem blood is thought to be affected by postmortem changes. Use of vitreous humor has been restricted by the available sample volume and instrument sensitivity. However, the advent of combined screening and quantitative methodologies using liquid chromatography-high-resolution mass spectrometry makes analysis of vitreous humor possible. This study examines an existing combined screening and quantitative methodology to determine if it is suitable for use with vitreous humor. Analysis of standard solutions containing 48 compounds showed % difference between expected and measured values in the range -15.59 to 20.81, -15.73 to 18.34, -14.32 to 19.77, and -19.90 to 19.78 for very low, low, mid and high range standard solutions respectively. Intraassay %CV was in the range 0.93 to 10.10, 1.35 to 15.19, 3.07 to 11.56, and 2.04 to 8.29 and interassay %CV was 0.96 to 17.40, 3.68 to 17.03, 3.94 to 17.12, and 4.87 to 16.55. Limits of quantitation range from 0.002 to 0.5 and limits of detection from 0.0008 to 0.06 mg/L. There was no significant interference from ion suppression or isobaric compounds and very little carryover. Dilution 1:2, 1:5 and 1:10 with vitreous humor gave acceptable results. Comparison of screening results from 129 postmortem cases showed that most compounds detected in blood and/or urine were also detected in vitreous humor. Compounds more readily detected in vitreous humor included 6-monoacetylmorphine, cocaine, codeine, dihydrocodeine, olanzapine, desmethylzopiclone, diazepam, cocaethylene, and desmethylmirtazapine. Compounds more readily identified in blood and/or urine included desmethylsertraline, EDDP, nordiazepam, papaverine, paracetamol, and morphine. The assay is suitable for screening and quantitation of drugs and their metabolites in vitreous humor and can be used where blood and urine are unavailable, or where the analysis of vitreous humor may provide useful information.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"645-654"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208527","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}
James A Goebl, Forch Zhao, Jasmine Zhong, Christopher Green, Sean Han
{"title":"Evaluation of the iScreen™ urine test FUO drug screen cup for detection of 17 drugs of abuse in urine.","authors":"James A Goebl, Forch Zhao, Jasmine Zhong, Christopher Green, Sean Han","doi":"10.1093/jat/bkaf062","DOIUrl":"10.1093/jat/bkaf062","url":null,"abstract":"<p><p>Drug overdoses are among the most common causes of death in the United States, with synthetic opioids such as fentanyl implicated in the majority of overdose fatalities in the last 10 years. As such, effective rapid assays capable of screening against large drugs of abuse panels that include synthetic opioids are critical tools for detecting drug abuse. The iScreen™ Urine Test FUO Drug Screen Cup (Abbott Laboratories) is a multiplexed lateral flow device designed for the preliminary qualitative screening drugs of abuse in urine for forensic applications, and can be used to simultaneously screen urine specimens for up to 17 different drugs of abuse, with multiple potential configurations of assays and cutoffs to support 22 different assay/cutoff combinations. This investigation focused on evaluating the performance of the iScreen™ Urine Test FUO Drug Screen Cup for analytical sensitivity, cross-reactivity characteristics for structurally-related compounds, and method comparison versus the gold standard method (GC-MS or LC-MS/MS). Analytical sensitivity testing demonstrated ≥95% accuracy for all 22 assays during evaluation against both negative and 3x cutoff positive control specimens, and all 22 assays achieved ≥89% concordance with the established reference methodologies in testing with positive and negative human urine specimens.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"705-712"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600485","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}
Valeria Aquilina, Francesco Paolo Busardò, José Luiz Costa, Simona Pichini
{"title":"Artificial intelligence as a linguistic aid: a call for fairness in scientific publishing.","authors":"Valeria Aquilina, Francesco Paolo Busardò, José Luiz Costa, Simona Pichini","doi":"10.1093/jat/bkaf092","DOIUrl":"10.1093/jat/bkaf092","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"734-735"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368034","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}
Marco Ballotari, Michael T Truver, Nayana A Sojin, Rhea Parimoo, Lauren A Agliano, Jennifer L Hoyer, Amie J Goodin, Deepthi S Varma, Chris W Chronister, Kay Roussos-Ross, Bruce A Goldberger
{"title":"Analysis of cannabinoids and semi-synthetic cannabinoids in authentic breastmilk samples by liquid chromatography-tandem mass spectrometry.","authors":"Marco Ballotari, Michael T Truver, Nayana A Sojin, Rhea Parimoo, Lauren A Agliano, Jennifer L Hoyer, Amie J Goodin, Deepthi S Varma, Chris W Chronister, Kay Roussos-Ross, Bruce A Goldberger","doi":"10.1093/jat/bkaf047","DOIUrl":"10.1093/jat/bkaf047","url":null,"abstract":"<p><p>Marijuana (cannabis) is generally considered the most frequently misused substance during pregnancy. The prevalence in the use of either medical or non-medical marijuana for relief of pregnancy-related symptoms is increasing, as well as the use of cannabis-related products containing cannabidiol (CBD) and semi-synthetic cannabinoids (SSCs). Δ9-tetrahydrocannabinol (THC) and CBD are highly lipophilic substances and will readily pass into breastmilk upon ingestion. The solubility of THC and CBD in lipids poses significant analytical challenges in extracting and identifying these substances in breastmilk. The aim of this study was to develop a new and sensitive assay utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the detection of cannabinoids in breastmilk. The method was optimized to quantitate Δ8-THC, Δ9-THC, cannabigerol (CBG), CBD, and cannabidiolic acid (CBDA) and validated with the guidance of the American Academy of Forensic Sciences Standards Board (ASB) Standard 036. The assay was then used to analyze breastmilk samples (N = 57) collected postpartum from female patients enrolled in a study assessing use behaviors of medical marijuana, non-medical marijuana, and CBD. All analytes passed validation criteria. Calibration curves for all analytes ranged 0.5-400 ng/mL, with the LOD and LLOQ of the method set at the lowest calibrator concentration. Δ9-THC was quantitated in 19 samples (33.3%) with a concentration range of 0.5-291 ng/mL. Δ8-THC was detected in one sample (1.8%) at 0.8 ng/mL, while CBD was observed in 3 samples at a concentration <LLOQ, and quantitated in only one sample (1.8%) also at a concentration of 0.8 ng/mL. CBG was detected in 7 samples (12.2%) with a concentration range of 0.6-12.9 ng/mL, and at a concentration <LLOQ in 12 samples. This study presents a sensitive method for the analysis of cannabinoids in breastmilk to support the follow-up assessments of marijuana and CBD use during pregnancy and postpartum.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"559-566"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142654","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}
Taylor L Yates, Justin L Poklis, Alaina K Holt, James H Fleming, Ciena Bayard, Stephen A Raso, Michelle R Peace
{"title":"Cross-reactivity in urine of 53 cannabinoid analogs and metabolites using a carboxylic acid enzyme-linked immunosorbent assay (ELISA) and homogenous enzyme immunoassay (HEIA) kit and immunalysis synthetic cannabinoid HEIA kits.","authors":"Taylor L Yates, Justin L Poklis, Alaina K Holt, James H Fleming, Ciena Bayard, Stephen A Raso, Michelle R Peace","doi":"10.1093/jat/bkaf055","DOIUrl":"10.1093/jat/bkaf055","url":null,"abstract":"<p><p>Advancing knowledge of endocannabinoid receptor agonists and the federal legalization of hemp has created a cannabinoid market of naturally abundant phytocannabinoids to a wide array of semi-synthetic and synthetic cannabinoid analogs. Public safety and toxicological concerns exist from lack of regulation, limited pharmacological and metabolomic data, and minimal knowledge of detection ability. Structural similarities of the cannabinoid analogs may allow detection on immunoassays including enzyme-linked immunosorbent assays (ELISA) and homogenous enzyme immunoassays (HEIA), screening platforms in forensic toxicology laboratories for rapid presumptive testing. The cross-reactivity of 27 cannabinoid analogs and 26 commercially available metabolites was evaluated using the Medica EasyRA Enzymatic Immunoassay Analyzer with the Immunalysis Cannabinoids (THC) and Synthetic Cannabinoids 1-3 kits. These analogs were also evaluated using the Dynex DSX Automated ELISA System with the OraSure Technologies Cannabinoids Intercept Microplate EIA. The cannabinoid kits target 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH) at a 50 ng/mL cutoff, and the synthetic cannabinoid kits target the N-pentanoic acid metabolite of JWH-018, UR-144, and AB-PINACA at a 10 ng/mL cutoff. Cross-reactivity was evaluated at concentrations of 20, 50, 100, 500, and 1000 ng/mL in urine in triplicate. Absence of cross-reactivity at 1000 ng/mL was considered undetectable. No cross-reactivity was detected on the synthetic cannabinoid kits. Cross-reactivity to Δ9-THCCOOH kits was variable with Δ8-THCCOOH and R-HHCCOOH cross-reacting at the cutoff on the ELISA, with several additional phase I metabolites cross-reacting at 100 ng/mL on both platforms. Analogs lacking the Δ9-THC tricyclic structure and pyran ring cyclization including cannabidiol were undetectable. Alicyclic bond location and alkyl chain length variably affected cross-reactivity, with alkyl lengths 2-4 having increased cross-reactivity comparatively. Compound chirality was also observed to effect instrumental response, with the ELISA having increased cross-reactivity and instrumental response to R-isomers. As knowledge and prevalence of analogs increases, it is crucial to understand the impact on utilized testing platforms.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"587-593"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511986","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}
Hope Smiley-McDonald, Sean Wire, Nichole D Bynum, Katherine M Bollinger, Kelly A Keyes, Jeri D Ropero-Miller
{"title":"Toxicology testing in the USA: what the 2018 census of medical examiner and coroner offices tells us.","authors":"Hope Smiley-McDonald, Sean Wire, Nichole D Bynum, Katherine M Bollinger, Kelly A Keyes, Jeri D Ropero-Miller","doi":"10.1093/jat/bkaf044","DOIUrl":"10.1093/jat/bkaf044","url":null,"abstract":"<p><p>In 2021, the U.S. Bureau of Justice Statistics (BJS) published results for the 2018 Census of Medical Examiner and Coroner Offices (CMEC) that provided an update on the medicolegal death investigation system in the USA. The 2018 Census collected data regarding toxicology service provisions, staffing, infrastructure, and practices, some of which were not included in the 2021 published BJS report from more than 1600 responding medical examiner/coroner offices (MECs). The 2018 CMEC was conducted from June 2019 through March 2020 by mail, online, and email. Toxicology-related CMEC data were obtained from BJS's publicly accessible dataset and evaluated in this study. Results from this study include information on toxicology service capability across MECs, including the number and salary of forensic toxicologists, toxicology retention time schedules, laboratory accreditation, professional certification, drug screening practices at the death scene, and whether they request confirmation testing. Overall, internal capabilities for toxicology testing were rare in 2018, with only 78 MECs (5.9%) reporting this function. Large MECs, serving a population of 250 000 or more, comprised about 15% of MECs that responded to the toxicology testing questions, with the rest being evenly divided between MECs that serve small (<25 000) and medium-sized (25 000-249 999) populations. Overall, 57.4% (n = 761) of MECs indicated that their forensic toxicology testing strategy has changed because of the increase in drug-related deaths, 53.9% of MECs (n = 715) perform drug screening tests, and 95.1% (n = 674) confirmed these tests with laboratory toxicology testing. Less than half of MECs reported that they had a toxicology specimen retention schedule (45.3%) or a computerized case management system (44.8%). These data are key to understanding (i) postmortem toxicology policies and practices, (ii) how these practices have evolved, (iii) MEC infrastructure, and (iv) the national importance of these data considering the ongoing drug overdose crisis.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"542-550"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132344","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}
Laura M Labay, Kari M Midthun, Sherri L Kacinko, Donna M Papsun
{"title":"Drug identification in biologicals on clothing, bedding, and other materials.","authors":"Laura M Labay, Kari M Midthun, Sherri L Kacinko, Donna M Papsun","doi":"10.1093/jat/bkaf057","DOIUrl":"10.1093/jat/bkaf057","url":null,"abstract":"<p><p>Toxicology testing is an integral component of postmortem, drug-facilitated crime, and driving under the influence investigations. Recommendations pertaining to traditional matrices, sample amounts, and collection container types are well documented in the literature and guidance documents. However, not all cases have traditional toxicological specimens available (e.g. blood with a fluoride additive), and thus require nontraditional toxicology test options. In these cases, a forensic laboratory is contacted to determine if nontraditional objects, such as clothing, bedding, automotive, personal hygiene, or household items, stained with biological material, are suitable for analysis. Comprehensive method validation, as required for routine toxicology tests, is not practical to complete for these items, but this should not deter the toxicology laboratory from taking on this work. Herein, we describe a developed and implemented process for qualitative analysis of biological fluids on/in objects, which ensures the robustness and reliability of reported results. The specific procedures used, which include sample preparation, the incorporation of specialized quality control samples made from the items themselves, analytical acceptance criteria, and reporting considerations are thoroughly detailed. Positive findings from cases were obtained for a variety of drugs, encompassing illicit, prescription, novel psychoactive substances, and over-the-counter medications. Some examples include identification of zolpidem from vomit on clothing; cocaine, cocaine metabolites, levamisole, codeine, acetaminophen, and caffeine in stains on bedding; and diphenhydramine, doxylamine, and dextromethorphan in stains on a mattress pad cover. This methodology is fit-for-purpose and suitable for the toxicological investigation of these unique specimens without any significant limitations. This testing process may be used to identify past drug exposure, associate drug exposure to a particular location or scene, and/or provide insight into an event when a missing person has not been found.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"603-608"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528061","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}
Laura W Friederich, Dani C Mata, Sandra C Bishop-Freeman
{"title":"Tizanidine in postmortem forensic cases.","authors":"Laura W Friederich, Dani C Mata, Sandra C Bishop-Freeman","doi":"10.1093/jat/bkaf056","DOIUrl":"10.1093/jat/bkaf056","url":null,"abstract":"<p><p>Alpha-2 adrenergic receptor agonists are established therapeutic medications that are used for conditions such as hypertension, pain disorders, muscle relaxation, spasticity, opioid withdrawal, insomnia, and sedation. While forensic toxicologists may be familiar with more common alpha receptor agonists, tizanidine is a less frequently identified compound, with limited published data available regarding antemortem and postmortem concentrations. Tizanidine therapeutic concentrations found in plasma are reported in the range of 0.0025-0.025 mg/L, although CYP1A2 inhibitors can significantly raise tizanidine levels in the body, thereby increasing the risk of dose-related toxicity. Additionally, imidazoline receptor activity is an underappreciated contributor to the mechanism of action and potential for adverse effects of this drug. Due to its high potency, tizanidine may be missed by forensic laboratories that are not targeting this drug or carefully inspecting untargeted data for its presence. In this study, 18 postmortem cases involving tizanidine are reviewed to improve the understanding of its forensic toxicological profile. These cases have been divided into categories as ruled by the certifying pathologist of \"Suicide\" involving tizanidine (N = 8, mean 6.2 mg/L and median 0.77 mg/L) and \"Accident\" involving tizanidine (N = 4, mean 0.86 mg/L and median 0.89 mg/L), and additionally a category of \"Incidental\" (N = 6, mean 0.35 mg/L and median 0.035 mg/L). Comparison of tizanidine concentrations to those in example cases such as this dataset can assist postmortem forensic toxicologists and pathologists in distinguishing therapeutic postmortem concentrations from toxic/lethal concentrations. However, consideration of scene details and totality of case investigation is essential when determining cause and manner of death.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"594-602"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505691","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}
Charles Perkins, Corissa Rodgers, Peter Stout, Dayong Lee
{"title":"Evaluation of sevoflurane interference with forensic blood ethanol analysis, including sevoflurane stability, and an authentic case.","authors":"Charles Perkins, Corissa Rodgers, Peter Stout, Dayong Lee","doi":"10.1093/jat/bkaf058","DOIUrl":"10.1093/jat/bkaf058","url":null,"abstract":"<p><p>Sevoflurane, a volatile anesthetic routinely used in clinical settings, was investigated to determine the extent of its interference with in-house forensic blood ethanol analysis. This potential interference could have a significant impact on the analysis and subsequently the interpretation of ethanol in human performance antemortem forensic toxicology casework (e.g. Driving While Under the Influence (DWI) cases). Aqueous samples with ethanol concentrations spanning 0.02-0.40 g/100 mL were fortified with sevoflurane and analyzed using two different dual-column headspace--gas chromatography with flame ionization detection instruments. Sevoflurane was found to elute as an interference peak near ethanol on column 1 (BAC1) and co-elute with ethanol on column 2 (BAC2); the differences were due to the column chemistries. Analyte identification and quantification acceptance criteria monitored included peak-to-valley ratio (resolution) and percent difference between individual column concentrations and the average value of both column concentrations. A 2023 DWI case exhibited potential sevoflurane interference and demonstrated the importance of ethanol reporting acceptance criteria for detecting such interference. In the majority of experiments with sevoflurane and ethanol present in the samples, sevoflurane presence caused failing acceptance criteria to report ethanol results, but if acceptance criteria were met, the ethanol concentration was slightly elevated. An additional sevoflurane stability study showed that the highly volatile sevoflurane could evaporate between analysis and re-analysis of blood samples due to additional tube openings. The decrease of sevoflurane was monitored at each opening of the tube using relative peak areas. HFSC re-analyzes suspected sevoflurane samples, as the additional tube openings could allow sevoflurane to evaporate.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"609-614"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528062","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}