Toxicologie Analytique et Clinique最新文献

{"title":"The potential role of extracorporeal membrane oxygenation in the management of aluminum phosphide-poisoned patients: A series of 10 cases","authors":"Rabab Abdulmoez Amin Eltokhy ,&nbsp;Shimaa Ahmed Alsaeed ,&nbsp;Akram Mohamed Abd El Bary ,&nbsp;Mahmoud Saad Nwar ,&nbsp;Mohamed Yosri Mohamed ,&nbsp;Bassant Abdelazeim ,&nbsp;Doaa Tawfik ,&nbsp;Amal Salama Mahmoud Mahmoud","doi":"10.1016/j.toxac.2024.10.004","DOIUrl":"10.1016/j.toxac.2024.10.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Aluminum phosphide pesticides have become a popular way of committing suicide in Egypt. Owing to the lack of a particular antidote, the management of aluminum phosphide toxicity is primarily supportive, so the mortality associated with aluminum phosphide poisoning is very high. This study aims to demonstrate the unique experience of using ECMO in the management of ALP poisoning at Cairo University.</div></div><div><h3>Methodology</h3><div>This case series included patients admitted to the Sheiref Mokhtar ICU Department, Kasr Al-Aainy Hospital, Cairo University, after ingestion of ALP tablets.</div></div><div><h3>Results</h3><div>All 10 patients were at high risk and clinically unstable, referred from the poisoning center, and did not respond to supportive management. Sixty percent of them were females, and 40% were males (with ages ranging from 13<!--> <!-->years to 40<!--> <!-->years). Of all the patients who received ECMO, 8 patients improved and were discharged, whereas 2 patients experienced cardiac arrest and died.</div></div><div><h3>Conclusion</h3><div>ECMO can prevent end-organ damage caused by ALP poisoning.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages 94-101"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remerciements aux relecteurs","authors":"","doi":"10.1016/S2352-0078(25)00117-9","DOIUrl":"10.1016/S2352-0078(25)00117-9","url":null,"abstract":"","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page 115"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update from the EU Early Warning System on new psychoactive substances","authors":"Thomas Néfau,&nbsp;Joanna De Morais,&nbsp;Simon Brandt,&nbsp;Ana Gallegos,&nbsp;Michael Evans-Brown,&nbsp;Gregorio Planchuelo,&nbsp;Roumen Sedefov","doi":"10.1016/j.toxac.2025.01.028","DOIUrl":"10.1016/j.toxac.2025.01.028","url":null,"abstract":"<div><h3>Aim</h3><div>The European Union Early Warning System on New Psychoactive Substances (EU EWS), operated by the EU Drug Agency (EUDA) is operational since 1997. It was the first regional early warning system to be established to monitor new psychoactive substances (NPS) and has been recognised as a model for national, regional and international early warning systems.</div></div><div><h3>Method</h3><div>The EU EWS rapidly detects, assesses and responds to health and social threats caused by NPS. Data collected and analysed include event based data on seizures by law enforcement, collected samples and serious adverse events linked to NPS. These data are complemented by annual reports, which include aggregated data on seizures and from poisonings.</div></div><div><h3>Results</h3><div>By September 2024, the EUDA was monitoring more than 980 NPS, 26 of which were first reported in 2023. The availability of NPS in Europe has reached a historic high, with more than 41 tons seized in 2023. This increase has been driven by a large increase in seizures of synthetic cathinones, in particular 3-CMC and 2-MMC, mostly trafficked from India. New threats continue to appear, including emergence of semi-synthetic cannabinoids (SSCs) and nitazenes. Since May 2022, 18 SSCs have been identified in Europe, underscoring the market's rapid evolution. They are sold openly in a broad range of consumer product forms, including vapes and edibles. While the available information on harms is limited, an outbreak of poisonings caused by edibles containing SSCs was reported by Hungary. Since 2022, there has been an increase in reports of nitazenes detections and poisonings in parts of Europe, and particularly in Estonia and Latvia. In addition, localised outbreaks of poisonings caused by nitazenes were reported by France and Ireland. The data also suggests an increase in the detection of fake medicines containing nitazene opioids.</div></div><div><h3>Conclusion</h3><div>Currently, the NPS market is characterised by complexity and increased integration with the market for established controlled drugs. The market is resilient and highly dynamic making it difficult to disrupt. Forensic and toxicological information sources are critically important for but there remains a need for investment in forensic, analytical and toxicological capacity. As of July 2024, the EUDA has a new mandate to implement and coordinate a network of laboratories with the aim of improving the detection capacity and knowledge of NPS, as well as the implementation of a European Drug Alert System (EDAS) for the detection and reporting of drug-related risks. The NPS market is still very dynamic in the EU and these new mechanisms (EUDA Laboratory network and EDAS) are aimed to further strengthen national and EU preparedness and response to NPS.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S22"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification of steroids in human serum for clinical research by TurboFlow using the new Transcend VTLX-1 UHPLC system","authors":"Claudio De Nardi,&nbsp;Joe Takarewski","doi":"10.1016/j.toxac.2025.01.092","DOIUrl":"10.1016/j.toxac.2025.01.092","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To implement an analytical method for quantifying eight steroids in human serum using TurboFlow online sample cleanup on the new Thermo Scientific™ Transcend™ VTLX-1 UHPLC system, coupled to a Thermo Scientific™ TSQ Altis triple quadrupole mass spectrometer. The study aims to compare the analytical performance with the same method run on a Thermo Scientific™ Transcend™ TLX-1 system in terms of chromatography, limits of quantification, accuracy, and intra-assay precision.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Liquid chromatography (LC) coupled with triple quadrupole mass spectrometry (MS/MS) is the preferred method for quantifying steroid hormones in biological matrices due to its superior specificity and sensitivity with low sample volumes. However, lab space and budget constraints often hinder its adoption.&lt;/div&gt;&lt;div&gt;To address these issues, we developed the new Thermo Scientific™ Transcend™ VTLX-1, an evolution of the Transcend TLX-1 UHPLC system. The VTLX-1 maintains the same functionalities but has a smaller footprint and a more affordable price. It supports online sample cleanup via TurboFlow or online SPE and UHPLC applications without online purification.&lt;/div&gt;&lt;div&gt;In this technical note, we compared the performance of the Transcend VTLX-1 and TLX-1 systems using a Thermo Scientific™ TSQ Altis triple quadrupole mass spectrometer. Serum samples, prepared by offline protein precipitation with internal standard addition, were injected into both systems. Detection was performed in SRM mode using the TSQ Altis with a HESI-II source in positive ionization mode. Method performance was evaluated based on chromatography, linearity, accuracy, and intra-assay precision using calibrators, controls, and internal standards from the ClinMass® Complete Kit for Steroids in Serum/Plasma from RECIPE Chemicals&lt;!--&gt; &lt;!--&gt;+&lt;!--&gt; &lt;!--&gt;Instruments GmbH.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;200&lt;!--&gt; &lt;!--&gt;μL aliquots of redissolved calibrators and controls were protein precipitated using 200&lt;!--&gt; &lt;!--&gt;μL of methanol containing six isotopically labelled internal standards, vortex-mixed and centrifuged. The supernatant was transferred to clean vials pending the injection. The same analytical method, including TurboFlow online sample cleanup, was used on the two UHPLC systems. The total runtime was 5.0&lt;!--&gt; &lt;!--&gt;minutes. Analytes and internal standards were detected in SRM acquisition mode on a TSQ Altis triple quadrupole mass spectrometer with heated electrospray ionization operated in positive ion mode.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results and Discussion&lt;/h3&gt;&lt;div&gt;Comparison of peak symmetry and intensity obtained on both front ends for the highest calibrator showed a superior peak symmetry for all analytes using the Transcend VTLX-1, thanks to the optimized fluidics. A linear response with 1/&lt;!--&gt; &lt;!--&gt;×&lt;!--&gt; &lt;!--&gt;weighting was obtained for all the analytes on both Transcend systems, with a correlation factor (R2) always above 0.9995. Experimen","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S59"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Panorama des produits de synthèse dérivés de la kétamine en France : usages et conséquences cliniques","authors":"Joelle Micallef ,&nbsp;Clémence Lacroix ,&nbsp;Nathalie Fouilhe ,&nbsp;Salim Mezaache ,&nbsp;Helène Peyriere ,&nbsp;Liselotte Pochard","doi":"10.1016/j.toxac.2025.01.080","DOIUrl":"10.1016/j.toxac.2025.01.080","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objectifs&lt;/h3&gt;&lt;div&gt;Le réseau français D’addictovigilance, via ses 13 centres D’addictovigilance, surveille et évalue les substances psychoactives y compris les NPS (nouveaux produits de synthèse) afin de déterminer leurs conséquences sanitaires chez l’homme. Piloté par l’ANSM, les connaissances fournies associées à une expertise pharmacologique constituent une aide à la décision publique afin d’informer usagers, professionnels de santé et proposer éventuellement des mesures réglementaires [Micallef J et al. Therapies 2019 Dec;74(6):579–590]. Décrire jusqu’au 31 décembre 2023 les données nationales d’Addictovigilance relatives aux NPS de la kétamine : 2-fluorodeschlorokétamine (2-FDCK), Deschlorokétamine (DCK), Deschloro-N-éthyl-kétamine (O-PCE), Fluorexetamine (FXE) et Hydroxetamine (HXE)&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Méthodes&lt;/h3&gt;&lt;div&gt;Ces données sont issues des dispositifs mis en place depuis plusieurs années : NotS (notifications spontanées c’est-à-dire des déclarations de cas cliniques), DRAMES (décès en relation avec l’abus de médicaments Et de substances via une collaboration avec les toxicologues analystes), OPPIDUM (observation des produits psychotropes illicites ou détournés de leur utilisation médicamenteuse ; données sur les consommations de produits psychoactifs par les patients pris en charge par les structures spécialisées en Addictologie).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Résultats&lt;/h3&gt;&lt;div&gt;Plusieurs résultats sont à souligner : (1) le signalement de cas d’addictovigilance en France (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;39) sur quasiment l’ensemble du territoire (11 des 13 centres d’addictovigilance, (2) une tendance à l’augmentation de ces cas (1 cas en 2017 versus 16 cas en 2023, (3) un panorama des produits dominé par la 2-FDCK (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;20 cas) et l’O-PCE (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;13 cas, 4/la sévérité des cas (26/39 soit 66 %) avec notamment 13 hospitalisations (dont 4 en réanimation) et 10 passages aux urgences. Les effets sont essentiellement neurologiques/neurovégétatif (dont mouvements anormaux (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;14), altération de l’état de conscience/coma (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;13) et agitation (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;8) et psychiatriques. L’analyse des caractéristiques des consommateurs montre qu’il s’agit majoritairement des hommes (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;37/39), d’âge médian de 29&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;10&lt;!--&gt; &lt;!--&gt;ans (1 mineur de 17&lt;!--&gt; &lt;!--&gt;ans). Quand les informations sont renseignées, 13 sujets ont déjà consommé des substances dissociatives (kétamine ou NPS).&lt;/div&gt;&lt;div&gt;L’analyse des modalités et contexte d’usage a permis d’identifier plusieurs profils de consommateurs :&lt;/div&gt;&lt;div&gt;i) Consommateurs expérimentaux ou occasionnels (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;5) ;&lt;/div&gt;&lt;div&gt;ii) Consommateurs NPS kétamine à visée « auto-thérapeutique » (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;3) ;&lt;/div&gt;&lt;div&gt;iii) Consommateurs réguliers (hors contexte auto-thérapeutique – ou non renseigné) (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;4) ;","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S52"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening des métaux : une place dans le bilan toxicologique à ne pas négliger","authors":"Bénédicte Lelievre ,&nbsp;Frédérique Beringue-Daures ,&nbsp;Aurélien Riodel ,&nbsp;Chloé Bruneau ,&nbsp;Gael Le Roux ,&nbsp;Alexis Descatha","doi":"10.1016/j.toxac.2025.01.042","DOIUrl":"10.1016/j.toxac.2025.01.042","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objectif&lt;/h3&gt;&lt;div&gt;Nous rapportons le cas d’une enfant de 3 mois (prématurée née à 26 SA &lt;!--&gt; &lt;!--&gt;+&lt;!--&gt; &lt;!--&gt; 5&lt;!--&gt; &lt;!--&gt;jours). Après 12 semaines d’hospitalisation, elle est rentrée au domicile puis est admise 1 semaine plus tard en état de choc avec détresse respiratoire, hypotonie et hypothermie. Parmi les différentes étiologies possibles, l’hypothèse d’une origine toxique a été explorée.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Méthode&lt;/h3&gt;&lt;div&gt;Un screening toxicologique par LC-HRMS, GC-MS a été réalisé sur les prélèvements sanguin et urinaire d’admission, puis un screening des métaux par ICP-MS après dilution au 1/20 dans une solution d’acide nitrique 0,5 % contenant les étalons internes (Rh, Re, Y, Eu, Ge, 10 μg/L). Devant les premiers résultats, des analyses de métaux ont été également effectuées sur les prélèvements de sang et d’urine de la maman ainsi que sur du lait maternel, du lait infantile et une huile alimentaire utilisés par le service et d’autres produits (crème, encens, produit capillaire importés) collectés lors d’une enquête environnementale au domicile des parents. Pour les composés solides, une étape préalable de minéralisation avec de l’acide nitrique a été effectuée avant analyse et quantification des métaux par une méthode dédiée (gamme de 0,25 à 40 μg/L). Les contrôles internes de qualité utilisés sont les Clincheck Trace Elements (plasma, urine) (Recipe®).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Résultats&lt;/h3&gt;&lt;div&gt;Les screenings n’ont pas mis en évidence la présence de médicaments ou substances autres. L’antimoine (Sb), le baryum (Ba) et l’étain (Sn) ont été détectés aux concentrations respectives de 16,7, 3,5 et 0,9 μg/L dans le plasma (J1) et de 2,1, 1266 et 300 μg/L dans l’urine (J0) de l’enfant. Les résultats urinaires ont été vérifiés sur un nouveau prélèvement effectué 12&lt;!--&gt; &lt;!--&gt;heures plus tard (Sb : 1,5 μg/L, Ba : 119,5 μg/L et Sn : 200 μg/L). L’analyse du lait maternel a montré la présence de métaux aux concentrations suivantes : Sb ; 0,77 μg/L, Ba ; 6,91 μg/L et Sn ; &lt; 0,25 μg/L, alors que les concentrations mesurées dans le lait en poudre et l’huile utilisés à l’hôpital sont inférieures à 0,25 μg/L. Les concentrations mesurées sur le prélèvement de plasma effectué chez la maman sont : 14,9 μg/L pour Sb, 2,9 μg/L pour Ba et 2,44 μg/L pour Sn, alors que les valeurs urinaires sont inférieures aux limites de quantification sauf pour Sb (1,6 μg/g créatinine). L’encens contenait &lt; 0,0005 ng/mg de Sb, 11,3 ng/mg de Ba et 0,028 ng/mg de Sn. L’analyse du beurre de karité et du produit capillaire a mis en évidence une concentration de Ba de 0,95 ng/mg pour le produit capillaire. À titre de comparaison, la concentration de Ba mesurée dans un échantillon de Lamiderm était de 0,74 ng/mg.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;La maman a expliqué qu’elle faisait brûler de l’encens tous les 2 jours dans la chambre de l’enfant pour purifier l’air. L’enfant est une grande prématurée, avec notamment une immaturité pulmonaire. L’évolution cliniqu","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S30"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-resolution mass spectrometry screening in forensic toxicology","authors":"Marta Concheiro-Guisan ,&nbsp;Miriam Blanco Ces ,&nbsp;Elena Lendoiro","doi":"10.1016/j.toxac.2024.11.008","DOIUrl":"10.1016/j.toxac.2024.11.008","url":null,"abstract":"<div><h3>Objective</h3><div>This presentation aims to introduce high-resolution mass spectrometry (HRMS) screening techniques to new users with forensic toxicology applications.</div></div><div><h3>Introduction</h3><div>HRMS is becoming an increasingly used technique in forensic toxicology. This technique offers essential advantages compared to classic screening techniques in toxicology, such as immunoassays and gas chromatography-mass spectrometry. HRMS has increased specificity, sensitivity, and versatility. It can be employed in targeted screening, suspect screening, tentative identification, structure elucidation, and quantitative and confirmation methods.</div></div><div><h3>Methods</h3><div>This presentation will explore all the steps involved in developing, employing, and validating HRMS screening techniques, including sample preparation procedures, chromatographic separation, HRMS instrumentation and data acquisition modes, data analysis and interpretation, and validation parameters.</div></div><div><h3>Results and discussion</h3><div>In this screening technique, biological samples must be extracted to remove interferences and matrix components that may affect the analysis and instrument performance (downtime). The sample preparation should be unspecific to avoid losing analytes while still removing matrix components. Protein precipitation and dilute-and-shoot procedures are frequently used. Regarding chromatographic separation, reversed-phase columns such as C18 or phenylhexyl and mobile phases with formic acid, methanol, or acetonitrile are preferred. The gradient should be wide enough to allow the elution of compounds with different polarities. The current instrumentation combines a quadrupole (Q) technology with high-resolution TOF (QTOF) or orbitrap (QOT) mass filters, allowing the use of tandem mass spectrometry (MS/MS) detection modes. Data acquisition can be performed in data-dependent (DDA) or data-independent (DIA) mode, depending on the selection or not of a specific precursor before performing a product ion scan. DDA is commonly used in targeted screening and suspect screening, and DIA in non-target analysis. DDA data analysis usually is easier and faster than DIA. HRMS screening methods must be validated; however, their validation should include specific parameters of interest for this technique, such as inter-day reproducibility of the mass spectra that may affect library match and incurred sample reanalysis.</div></div><div><h3>Conclusion</h3><div>HRMS is becoming the state-of-the-art technique for screening analysis in clinical and forensic toxicology. This presentation will help toxicologists new to HRMS understand the technique and its advantages and address practical issues in its application.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S62"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double faux positif « amphétamines » urinaire (méthode de dépistage immunochimique et criblage toxicologique par CL-SMHR) chez une patiente traitée par Solriamfétol (SUNOSI)","authors":"Corentin Grenier ,&nbsp;Camille Richeval ,&nbsp;Alexandr Gish ,&nbsp;Marie Lenski ,&nbsp;Florian Hakim ,&nbsp;Benjamin Hennart ,&nbsp;Nicolas Beauval ,&nbsp;Delphine Allorge ,&nbsp;Jean-Michel Gaulier","doi":"10.1016/j.toxac.2025.01.087","DOIUrl":"10.1016/j.toxac.2025.01.087","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objectifs&lt;/h3&gt;&lt;div&gt;En réponse à des demandes de recherche large de xénobiotiques pour le service de neurophysiopathologie du sommeil, le laboratoire de toxicologie du CHU de Lille réalise en routine des criblages toxicologiques dans l’urine par des méthodes immunoenzymatiques (CEDIA) et par chromatographie liquide avec détection par spectrométrie de masse haute résolution (CL-SMHR) dont la bibliothèque de référence comprend 1800 molécules [Grenier, ToxAC, 2024, 36, S40]. Nous rapportons un résultat urinaire positif pour les amphétamines [détection positive par méthode immunoenzymatique et détection de 2-Aminoindane (2-AI) par CL-SMHR] chez une patiente traitée par solriamfétol. Une femme, 30&lt;!--&gt; &lt;!--&gt;ans, se présente en Hôpital de jour de Neurophysiologie du sommeil dans le cadre d’un suivi de narcolepsie de type 1 diagnostiqué en 2014. Un bilan de biologie est demandé systématiquement comprenant un dépistage des toxiques urinaires et un criblage toxicologique urinaire par CL-SMHR. Les résultats révèlent une positivité du dépistage amphétaminique urinaire ainsi que la présence de 2-AI par le criblage toxicologique en CL-SMHR. Dans le cadre de sa narcolepsie, la patiente a été traitée par modafinil de 2014 à Avril 2023, puis par solriamfétol depuis. L’anamnèse n’est pas en faveur de l’hypothèse de conduites addictives, ni de prises de NPS, et des bilans toxicologiques antérieurs à 2023 n’avaient jamais mis en évidence de toxiques.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Méthodes&lt;/h3&gt;&lt;div&gt;À partir d’une solution pure de solriamfétol et d’une solution de 2-AI mises en solution dans l’urine, une gamme de calibrage (0,5–1000&lt;!--&gt; &lt;!--&gt;mg/L) a été réalisée, et soumise (1) à la méthode immunoenymatique CEDIA sur un AU480 (BECKMAN-COULTER), et (2) à notre méthode de criblage toxicologique par CL-SMHR sur un Xevo G2XS QTOF. Une étude du métabolisme par microsomes hépatiques humains a également été réalisées par CL-SMHR [Gish, DTA,2022,9,994–997].&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Résultats&lt;/h3&gt;&lt;div&gt;La concentration urinaire positivant le test immunoenzymatique est de 5&lt;!--&gt; &lt;!--&gt;mg/L pour le solriamfétol et de 100&lt;!--&gt; &lt;!--&gt;mg/L pour le 2-AI, et l’analyse par CL-SMHR du solriamfétol pur révèle un pic de m/z 195,1134 mais également un autre pic de m/z 134,0970 identique au [MH+] du 2-AI présent dans la bibliothèque de référence. Cependant, les temps de rétention chromatographiques diffèrent légèrement entre les molécules (1,74&lt;!--&gt; &lt;!--&gt;min pour le solriamfétol versus 1,84&lt;!--&gt; &lt;!--&gt;min pour le 2-AI). Les spectres de masse (avec et sans fragmentation) sont également différents, objectivés par des rapports ion fils/ion parent différents. L’étude du métabolisme du solriamfétol n’amène pas d’éléments différentiels évident par rapport au 2-AI. Le solriamfétol (SUNOSI), chlorhydrate de carbamate de (2R)-2-amino-3-phénylpropyle, a obtenu son AMM en 2020 pour améliorer l’éveil et réduire la somnolence diurne chez les patients adultes atteints de narcolepsie. Son analogie structurale ave","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages S56-S57"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to respond to real time drugs-alerts? Comparison between French and Belgian early warning systems","authors":"Sabrina Cherki ,&nbsp;Margot Balcaen","doi":"10.1016/j.toxac.2025.01.021","DOIUrl":"10.1016/j.toxac.2025.01.021","url":null,"abstract":"<div><h3>Aim</h3><div>The rise of new psychoactive substances (NPS) in recent years has created an unpredictable and volatile drug market, underscoring the need for effective preparedness and rapid public health responses. Each EU Member State currently operates its own system for detecting and addressing emerging drug threats. Sharing best practices in threat assessment, risk communication, and other public health strategies, alongside national experiences with the EU Early Warning System (EWS) managed by the European Drug Agency (EUDA), is crucial for improving coordination in responding to cross-border drug issues. France and Belgium, as neighboring countries, face common challenges related to the emergence of new synthetic opioids. This presentation aims to examine and compare the organizational structures in France and Belgium for addressing future drug-related threats, using nitazenes as a case study.</div></div><div><h3>Method</h3><div>Nitazenes are a newly emerging class of synthetic opioids, monitored as NPS by the EUDA's EWS. These opioids feature a benzimidazole core in their chemical structure and are characterized by a high affinity and potency at opioid receptors, far surpassing that of heroin. As such, they pose a significant risk of overdose, whether from intentional use or accidental exposure due to misrepresentation of substances. The ongoing outbreak of acute poisonings and seizures of nitazenes will be used to illustrate the operation and collaboration of the Belgian and French Early Warning Systems.</div></div><div><h3>Results</h3><div>The Belgian Early Warning System employs foresight approaches to enhance preparedness for a wide range of drug-related threats. Continued collaboration with stakeholders and the implementation of ad hoc reporting mechanisms has improved monitoring efforts. Legislative measures include the specific listing of nitazenes in Belgian law. In France, updates have been made to the national early warning procedures, and intensive monitoring is facilitated through the SINTES national program, which focuses on analytical toxicology of drug samples provided by users. Additionally, a generic ban on benzimidazoles has been enacted in French law as of July 2024.</div></div><div><h3>Conclusion</h3><div>Both Belgium and France have similarly structured early warning systems for responding to emerging drug threats. In Belgium, nitazenes are mostly detected through seizures, while in France, the substance has been implicated in several outbreaks of acute poisoning. Ongoing monitoring of cross-border threats and regular communication between the two countries regarding national drug markets are key components of joint public health responses to the emergence of new psychoactive substances.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S18"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro metabolism of flubrotizolam, a thieno-triazolo designer benzodiazepine","authors":"Jeremy Carlier ,&nbsp;Prince Sellase Gameli ,&nbsp;Johannes Kutzler ,&nbsp;Diletta Berardinelli ,&nbsp;Volker Auwärter ,&nbsp;Francesco Paolo Busardò","doi":"10.1016/j.toxac.2025.01.026","DOIUrl":"10.1016/j.toxac.2025.01.026","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Aim&lt;/h3&gt;&lt;div&gt;Prescription benzodiazepines are widely used for their anxiolytic effects, but their addictive potential and the rise of designer benzodiazepines, a subgroup of new psychoactive substances (NPSs), pose significant health concerns. Flubrotizolam, a highly potent thieno-triazolo NPS benzodiazepine structurally similar to brotizolam, was first identified in 2021 and has been associated with impaired driving and drug abuse. Its similarity to brotizolam suggests extensive hepatic metabolism, with metabolites potentially serving as markers of consumption in biological specimens. Profiling its metabolism is critical to improving the detection of flubrotizolam-positive cases in clinical and forensic toxicology.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;Flubrotizolam was incubated for 3&lt;!--&gt; &lt;!--&gt;h with cryopreserved 10-donor-pooled human hepatocytes following a well-established protocol &lt;span&gt;&lt;span&gt;[1]&lt;/span&gt;&lt;/span&gt;. Incubations were also performed as controls: without the drug, without the hepatocytes, or by interrupting metabolic reactions immediately after mixing the drug with hepatocytes. The incubates were analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) after protein precipitation and centrifugation, and the LC-HRMS/MS data was screened with Compound Discoverer (Thermo Scientific). LC-HRMS/MS analysis and software-aided data mining were supported by in silico metabolite predictions with GLORYx freeware (Hambourg University, Germany). Additionally, the 3&lt;!--&gt; &lt;!--&gt;h incubate was re-analyzed after β-glucuronidase hydrolysis to clarify the structure of specific phase II metabolites.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Although flubrotizolam signal intensities were similar in 0 and 3&lt;!--&gt; &lt;!--&gt;h incubates, six metabolites were detected with two major phase I metabolites accounting for 80% of the total metabolites’ signal. These two metabolites were produced via hydroxylation at carbon 6 of the diazepam ring or carbon 9 of the triazole ring, yielding 6-hydroxyflubrotizolam or α-hydroxyflubrotizolam, respectively. The (6R)- and (6S)-hydroxy diastereoisomers were likely formed but not chromatographically resolved. Additionally, four N- or O-glucuronides were identified, albeit with low signal intensity.&lt;/div&gt;&lt;div&gt;The results were consistent with the in vivo human metabolism of brotizolam, the chloro-phenyl analogue of flubrotizolam, and other thieno-triazolo benzodiazepines &lt;span&gt;&lt;span&gt;[2]&lt;/span&gt;&lt;/span&gt;. Brotizolam 6- and α-hydroxylation are mainly catalyzed by cytochrome P450 3A4 isozymes &lt;span&gt;&lt;span&gt;[3]&lt;/span&gt;&lt;/span&gt;, and flubrotizolam might follow the same pathway. Flubrotizolam remained largely unmetabolized after 3&lt;!--&gt; &lt;!--&gt;h of incubation, possibly indicating low clearance and prolonged pharmacological effects in vivo. This aligns with in silico structure-activity relationship simulations performed by Catalani et al. &lt;span&gt;&lt;span&gt;[4]&lt;/span&gt;&lt;/span&gt;. Additionally, if 6- and α-hydroxyflubrotizolam","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S21"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}