Journal of analytical toxicology最新文献

{"title":"N-Ethylhexedrone: A very long and bad trip! A case series.","authors":"Sandrine Lefeuvre, Camille Richeval, Jeremy Lelong, Nicolas Venisse, Luc Humbert, Bertrand Brunet","doi":"10.1093/jat/bkae040","DOIUrl":"10.1093/jat/bkae040","url":null,"abstract":"<p><p>N-ethylhexedrone (NEH) is a new cathinone derivative with, currently, low toxicokinetic and toxicodynamic knowledge. We present three documented clinical cases of NEH intoxication with plasma and urine concentrations. A thorough search for metabolites was performed. The three patients were admitted to the emergency department, and two out of the three were hospitalized for an extended period. While recovering from the drug effects, 12-24 h after nasal intake of New Psychoactive Substance (NPS), the patients described the following disorders: anxiety, feelings of persecution, asthenia, anhedonia, abulia, psychomotor slowing and loss of consciousness. NEH was identified in all samples by liquid chromatography-high resolution mass spectrometry (LC-HRMS), and quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). Quantitative analysis showed decreasing concentrations over time: for Case 1, from 97.2 (Day 1, D1) to 0.7 (Day 7, D7) µg/L for plasma, and from 724 (D1) to 0.5 (D7) µg/L for urine. NEH concentration of 7.9 µg/L was found in the plasma collected at admission for Case 2. For Case 3, concentrations ranging from 49 (D1) to 1.8 (D7) µg/L in plasma, and from 327.3 (Day 6, D6) to 116.8 (D7) µg/L in urine were found. NEH was no longer detected in the urine sample at Day 10. Elimination half-life was estimated at 19, and 28 hours in Patients 1 and 3, respectively. Four metabolites were identified in blood and urine: reduced NEH, dealkyl-NEH, reduced dealkyl-NEH and hydroxy-NEH. The cases presented highlight the long detectable lifetime of NEH. Characterization of the metabolites will allow better identification of the consumption of this drug. Serious adverse events can be observed after NEH consumption, as two out of the three patients required intubation and ventilation. A syndrome of inappropriate antidiuretic hormone secretion (SIADH) was also diagnosed. Two out of the three cases are notable because of the number of samples collected and because NEH was the only drug of abuse detected.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"507-513"},"PeriodicalIF":2.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093136","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":"Consumption of seasoning containing poppy seeds can cause codeine positive urine drug test results for pain management monitoring.","authors":"Larry A Broussard, Jeanne Carr, Jeffrey Hurst","doi":"10.1093/jat/bkae056","DOIUrl":"10.1093/jat/bkae056","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"523-525"},"PeriodicalIF":2.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468025","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":"Over-the-counter medications encountered in the postmortem pediatric population from 2010-2020.","authors":"Jennifer L Swatek, Stephanie M Marco, Kari M Midthun","doi":"10.1093/jat/bkae042","DOIUrl":"10.1093/jat/bkae042","url":null,"abstract":"<p><p>In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences (e.g., metabolic capabilities, body size, etc.) between the pediatric and adult populations. In particular, the administration of over-the-counter (OTC) medications needs careful consideration, as dosages given to the pediatric population (0 days-18 years), particularly those given to individuals <5 years of age, tend to be lower than those given to individuals closer to adulthood. Postmortem pediatric data from 11 years (2010-2020) was compiled. A total of 1413 positive cases contained one or more of the following common OTC medications: antihistamines (brompheniramine, chlorpheniramine, diphenhydramine, doxylamine and pheniramine), pain relievers (acetaminophen, naproxen, ibuprofen and salicylates), cold/flu medications (dextro/levomethorphan, guaifenesin, ephedrine and pseudoephedrine), gastrointestinal aids (dicyclomine and loperamide) and/or sleep aids (melatonin). Antihistamines, cold/flu medications and pain relievers are the most common classes of drugs encountered in the postmortem pediatric population. To evaluate trends, three main age groups were created: ≤5 years old (5 U, birth-5 years old), middle childhood (MC, 6-11 years old), and early adolescence (EA, 12-18 years old). When considering the data, it must be noted that many of these drugs may be co-administered in single and/or multi-drug formulations. In addition, some drugs may have a variety of uses, e.g. antihistamines may also be used as sleep aids. Of note, the prevalence of cases involving those aged 6-11 years old was far less than their younger and older pediatric counterparts. With the widespread availability of OTC medications, unintentional overdoses, recreational misuse and suicidal overdoses can occur in the vulnerable, pediatric population.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"473-481"},"PeriodicalIF":2.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070677","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":"Qualitative and quantitative determination of xylazine in oral fluid.","authors":"Matthew Levitas, Christopher Thomas, Corey Widman, Joseph DeColumna, Brandi Allgaier, Eric Conley, Troy deHagen, Isabela Freitas, Hannah Horvath, Bridget Lemberg, Dave Lemberg","doi":"10.1093/jat/bkae055","DOIUrl":"10.1093/jat/bkae055","url":null,"abstract":"<p><p>Xylazine has emerged in recent years as a dangerous adulterant in illicit fentanyl use, and methods for the detection of xylazine in toxicology panels are still lagging. We developed methods for the screening and quantitation of xylazine in oral fluid (OF), a popular testing medium due to its ease of collection and reflection of presence in blood for many classes of drugs. Enzyme-linked immunosorbent assays were employed for the rapid screening of xylazine directly from the collection device buffer with a cutoff of 1 ng/mL. Solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry facilitated the confirmation and quantification of xylazine as low as 0.1 ng/mL and a dynamic range of 0.1-25 ng/mL. Selectivity, ionization suppression, processed sample stability, and dilution effect were also assessed. The method was validated through the American National Standards Institute/American Academy of Forensic Sciences Standards Board (ANSI/ASB) Standard 036, first edition from 2019, and found to be accurate, precise, and robust. Living human subject OF samples collected within substance use disorder and therapeutic drug monitoring clinics received between September 2023 and January 2024, with the specific request to test for xylazine (n = 57), were screened. Presumptive positive samples were confirmed using the validated method. Xylazine confirmed living human subject OF sample concentrations ranged from 1.2 to 23.3 ng/mL.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"482-488"},"PeriodicalIF":2.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603668","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":"Brain homogenate stability for stimulant drugs.","authors":"Grayce Behnke, Teresa R Gray, Crystal Arndt","doi":"10.1093/jat/bkae058","DOIUrl":"10.1093/jat/bkae058","url":null,"abstract":"<p><p>Brain can be a useful specimen for toxicology testing as it is a protected and isolated organ with lower metabolic activity than other tissues, but there is currently no published data supporting the stability of stimulant drugs in prepared brain homogenates. Brain homogenates were evaluated to determine the stability of the following stimulant drugs: amphetamine, benzoylecgonine, bupropion, cocaethylene, cocaine, ephedrine, methylenedioxyamphetamine, methylenedioxymethamphetamine, methamphetamine, and phentermine. Four different homogenates were prepared at a 1:4 dilution with deionized water and fortified at 500 ng/mL of: cocaine without sodium fluoride, cocaine with 1% sodium fluoride, stimulant drugs other than cocaine without sodium fluoride, and stimulant drugs other than cocaine with 1% sodium fluoride. The fortified homogenates were aliquoted into 13 × 100-mm screw cap tubes and stored at room temperature (∼20°C), refrigerated (2-8°C), or frozen (<-5°C) and analyzed in triplicate on Days 0, 1, 3, 7, 14, 30, 60, and 90. Analytes were considered stable as long as the difference in analyte/internal standard response ratio from Day 0 was less than 20% and the peaks met qualitative acceptance criteria. All analytes were stable for up to 90 days when stored frozen with or without sodium fluoride and had variable stability at all other evaluated conditions.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"514-518"},"PeriodicalIF":2.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468023","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":"Electromembrane extraction of drugs of abuse and prescription drugs from micropulverized hair.","authors":"Maria Schüller, Marianne Skov-Skov Bergh, Stig Pedersen-Bjergaard, Elisabeth Leere Øiestad","doi":"10.1093/jat/bkae051","DOIUrl":"10.1093/jat/bkae051","url":null,"abstract":"<p><p>Hair analysis can provide chronological insights into past drug use for months to years after drug administration. In comparison to analyses from other biological matrices, such as blood and urine, sample pretreatment is often tedious and not environmental friendly. In this study, we present a more environmental friendly approach to hair analysis using micropulverized hair and electromembrane extraction for the efficient extraction of 15 drugs of abuse, prescription drugs, and metabolites from hair. The optimized extraction method, involving micropulverization, demonstrated comparable yields to the standard approach of cutting and overnight incubation. A 15-min extraction method using a commercial electromembrane extraction prototype was developed and validated according to forensic guidelines, using only 10 µL of organic solvent per sample. The final method, employing HPLC-MS-MS with a biphenyl column, exhibited good linearity, precision, and sensitivity. An AgreePrep assessment comparing the environmental impact of our method with the standard routine method, involving overnight incubation and conventional liquid-liquid extraction, was conducted. This is the first time micropulverized hair has been subjected to electromembrane extraction.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"489-498"},"PeriodicalIF":2.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436897","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":"LC-MS-MS quantification of Δ8-THC, Δ9-THC, THCV isomers and their main metabolites in human plasma.","authors":"Cristina Sempio, Jorge Campos-Palomino, Jelena Klawitter, Amy Harrison, Erica N Peters, Laura MacNair, Mehdi Haghdoost, Marcel Bonn-Miller, Shanna Babalonis, Marilyn A Huestis, Uwe Christians, Jost Klawitter","doi":"10.1093/jat/bkae048","DOIUrl":"10.1093/jat/bkae048","url":null,"abstract":"<p><p>In recent years, potential therapeutic applications of several different cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC), its isomer Δ8-THC and Δ9-tetrahydrocannabivarin (Δ9-THCV), have been investigated. Nevertheless, to establish dose-effect relationship and to gain knowledge of their pharmacokinetics and metabolism, sensitive and specific analytical assays are needed to measure these compounds in patients. For this reason, we developed and validated an online extraction high-performance liquid/liquid chromatography-tandem mass spectrometry (LC/LC-MS-MS) method for the simultaneous quantification of 13 cannabinoids and metabolites including the Δ8 and Δ9 isomers of THC, THCV and those of their major metabolites in human plasma. Plasma was fortified with cannabinoids at varying concentrations within the working range of the respective compound and 200 µL was extracted using a simple one-step protein precipitation procedure. The extracts were analyzed using online trapping LC/LC-atmospheric pressure chemical ionization-MS-MS running in the positive multiple reaction monitoring mode. The lower limit of quantification ranged from 0.5 to 2.5 ng/mL, and the upper limit of quantification was 400 ng/mL for all analytes. Inter-day analytical accuracy and imprecision ranged from 82.9% to 109% and 4.3% to 20.3% (coefficient of variance), respectively. Of 534 plasma samples following controlled oral administration of Δ8-THCV, 236 were positive for Δ8-THCV (median; interquartile ranges: 3.5 ng/mL; 1.8-11.9 ng/mL), 383 for the major metabolite (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabivarin (Δ8-THCV-COOH) (95.4 ng/mL; 20.7-328 ng/mL), 260 for (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (Δ9-THCV-COOH) (5.8 ng/mL; 2.5-16.1 ng/mL), 157 for (-)-11-hydroxy-Δ8-tetrahydrocannabivarin (11-OH-Δ8-THCV) (1.7 ng/mL; 1.0-3.7 ng/mL), 49 for Δ8-THC-COOH (1.7 ng/mL; 1.4-2.3 ng/mL) and 42 for Δ9-THCV (1.3 ng/mL; 0.8-1.6 ng/mL). We developed and validated the first LC/LC-MS-MS assay for the specific quantification of Δ8-THC, Δ9-THC and THCV isomers and their respective metabolites in human plasma. Δ8-THCV-COOH, 11-hydroxy-Δ8-THCV and Δ9-THCV-COOH were the major Δ8-THCV metabolites in human plasma after oral administration of 98.6% pure Δ8-THCV.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"499-506"},"PeriodicalIF":2.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248189","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":"Difficulties associated with the interpretation of postmortem toxicology.","authors":"Lilli Stephenson, Corinna Van Den Heuvel, Timothy Scott, Roger W Byard","doi":"10.1093/jat/bkae052","DOIUrl":"10.1093/jat/bkae052","url":null,"abstract":"<p><p>While postmortem (PM) toxicology results provide valuable information towards ascertaining both the cause and manner of death in coronial cases, there are also significant difficulties associated with the interpretation of PM drug levels. Such difficulties are influenced by several pharmacokinetic and pharmacodynamic factors including PM redistribution, diffusion, site-to-site variability in drug levels, different drug properties and metabolism, bacterial activity, genetic polymorphisms, tolerance, resuscitation efforts, underlying conditions, and the toxicity profile of cases (i.e. single- or mixed-drug toxicity). A large body of research has been dedicated for better understanding and even quantifying the influence of these factors on PM drug levels. For example, several investigative matrices have been developed as potential indicators of PM redistribution, but they have limited practical value. Reference tables of clinically relevant therapeutic, toxic, and potentially fatal drug concentrations have also been compiled, but these unfortunately do not provide reliable reference values for PM toxicology. More recent research has focused on developing databases of peripheral PM drug levels for a variety of case-types to increase transferability to real-life cases and improve interpretations. Changes to drug levels after death are inevitable and unavoidable. As such, guidelines and practices will continue to evolve as we further our understanding of such phenomena.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"405-412"},"PeriodicalIF":2.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293376","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":"Enantiomeric profile of amphetamines in seized drug samples and in blood of impaired drivers in Iceland: The rise of (R)-methamphetamine?","authors":"Adam E Bauer, Margret R Jakobsdottir, Kristin Olafsdottir","doi":"10.1093/jat/bkae039","DOIUrl":"10.1093/jat/bkae039","url":null,"abstract":"<p><p>Amphetamine (AMP) and methamphetamine (METH) use is increasing globally. Illegal AMP is generally a racemic mixture, whereas AMP-containing attention-deficit hyperactivity disorder drugs prescribed in Iceland consist of S-AMP. AMP is also a main metabolite of interest after METH intake. Distinguishing between legal and illegal AMP intake is vital in forensic toxicology. A chiral UPLC-MS-MS method was used to determine the enantiomeric profile of AMP and METH in circulation in Iceland by analysing blood samples from drivers suspected of driving under the influence of drugs (DUID) and seized drug samples from 2021 and 2022. All seized AMP samples (n = 48) were racemic, whereas all but one seized METH sample (n = 26) were enantiopure. Surprisingly, a large portion of the enantiopure METH samples was R-METH. DUID blood samples positive for AMP (n = 564) had a median blood concentration of 180 ng/mL (range 20-2770 ng/mL) and a median enantiomeric fraction (EFR) of 0.54 (range 0-0.73), whereas samples positive for METH (n = 236) had a median blood concentration of 185 ng/mL (range 20-2300 ng/mL) and a median EFR of 0.23 (range 0-1). The findings of this study show a significantly lower blood concentration in drivers with only S-AMP detected compared with when the R-isomer is also detected. No significant difference in blood concentration was detected between the sample groups containing S-METH, R-METH or both enantiomers. The occurrence of R-METH in both seized drug samples and DUID cases indicates a change in drug supply and a need for better scientific knowledge on R-METH abuse.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"456-462"},"PeriodicalIF":2.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943402","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 the ARK Diagnostics immunoassay for qualitative detection of xylazine in urine.","authors":"Patrick B Kyle, Christopher J Mattiello, Albert Hua, Joanne M Toohey, Warren R Korn, Alana Saldana-Reed, Douglas F Stickle","doi":"10.1093/jat/bkae043","DOIUrl":"10.1093/jat/bkae043","url":null,"abstract":"<p><p>Xylazine exposure is common in some US cities, but a commercial assay for routine laboratory testing for xylazine is not currently available. We evaluated a pre-release version of the ARK Diagnostics immunoassay for qualitative detection of xylazine/4-hydroxyxylazine in urine. Studies were conducted using either the semi-quantitative assay application (A. Roche Cobas 503 analyzer) or the qualitative assay application (B. Beckman Coulter AU480 analyzer). Study specimens consisted of deidentified patient urine samples submitted for routine drugs-of-abuse testing. Measurements of xylazine (X) were performed by LC-MS-MS to obtain X-NEGATIVE (X <10 ng/mL) and X-POSITIVE (X ≥10 ng/mL). The semi-quantitative ARK assay was calibrated with a 10 ng/mL cutoff for ARK-POSITVE. For (A): among 74 X-POSITIVE samples, there was 1 ARK-NEGATIVE result (false-negative rate = 1.4%); among 78 X-NEGATIVE samples by LC-MS-MS, there were 0% ARK-POSITIVE results (false-positive rate = 0%). For (B), among 74 X-POSITIVE samples, there were 0 ARK-NEGATIVE results (false-negative rate = 0%); among 78 X-NEGATIVE samples there was 1 ARK-POSITIVE sample (false-positive rate = 1.3%). Common sources of interferences were investigated without evidence of interference. The ARK xylazine/4-OH-xylazine immunoassay was found to be suitable for routine use in screening patient urine samples for presence of xylazine >10 ng/mL.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"468-471"},"PeriodicalIF":2.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157338","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}