Camille Paradis , Arnaud Courtois , Jules-Antoine Vaucel , Ingrid Blanc-Brisset , Cécile Record , Guillaume Grenet , Elisabete Gomes , Audrey Nardon , Natacha Louviaux , French PCC Research Group, Magali Labadie
{"title":"Acute thyroid hormone exposures in children: A French Poison Control Centers cohort study","authors":"Camille Paradis , Arnaud Courtois , Jules-Antoine Vaucel , Ingrid Blanc-Brisset , Cécile Record , Guillaume Grenet , Elisabete Gomes , Audrey Nardon , Natacha Louviaux , French PCC Research Group, Magali Labadie","doi":"10.1016/j.toxac.2024.09.020","DOIUrl":"10.1016/j.toxac.2024.09.020","url":null,"abstract":"<div><h3>Purpose</h3><div>Thyroid hormones are involved in many metabolic and physiological processes, including basal metabolism, thermoregulation, and heart rate; however, there is little information on acute exposure in children, with only a few cases reports or small cases series being available. Our study was undertaken to provide more information about the epidemiological and clinical course of L-thyroxine poisoning in a large pediatric population.</div></div><div><h3>Methods</h3><div>This multicenter historical cohort study was conducted using data from the French Poison Control Centers on the acute ingestion of thyroid hormone in children (0–18 years of age) between January 2018, 1st and December 2020, 31st.</div></div><div><h3>Results</h3><div>Of the 2,321 files analyzed, 1,307 cases were included. Toddlers (1–4 years) accounted for 72.8% of the cases. Oral ingestion was unintentional in 96% of the cases. The medicine was from a relative in 97.5% of cases. Only 10 (0.8%) children were symptomatic. No symptoms were reported below a dose of 6.6<!--> <!-->μg/kg and some patients remained asymptomatic up to an alleged dose of 500<!--> <!-->μg/kg. The symptoms reported were minor, transitory, and limited to tremor, agitation, diarrhea, vomiting, and tachycardia.</div></div><div><h3>Conclusion</h3><div>Acute L-thyroxine poisoning in children was mainly accidental (unintentional) and has only a few benign symptoms. The clinical outcome is good even if the alleged ingested dose is massive (up to 500<!--> <!-->μg/kg).</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages 88-93"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527190","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":"Intoxication grave par bêtabloquant et inhibiteurs calciques, apport de l’analyse dans la prise en charge du patient","authors":"Magali Labadie , Antoine Beurton , Nadège Castaing , Audrey Nardon , Christine Tournoud , Coralie Braganca","doi":"10.1016/j.toxac.2025.01.075","DOIUrl":"10.1016/j.toxac.2025.01.075","url":null,"abstract":"<div><h3>Objectifs</h3><div>Présenter un cas grave d’intoxication par des médicaments cardiotoxiques et discuter l’apport de l’analyse dans ce contexte.</div></div><div><h3>Méthodes</h3><div>Cas clinique : une femme de 57<!--> <!-->ans, traitée par fluoxétine alprazolam, amlodipine, bisoprolol est retrouvée comateuse, score de Glasgow 9, à 3<!--> <!-->h. Elle aurait pris la veille au soir (J0) 60 comprimés (cp) de bisoprolol 2.5, 20 cp de vérapamil LP 240, 15 cp d’alprazolam 0.5, 28 cp fluoxétine 20, et 9 cp de dapagliflozine. Elle est admise aux urgences à 4<!--> <!-->h (J1). À 6h50, elle présente une bradycardie à 20 battements par minute (bpm) avec pression artérielle (PA) imprenable. Elle est massée, intubée (low flow<!--> <!-->=<!--> <!-->15<!--> <!-->min) et sédatée. Elle est traitée par voie IV par noradrénaline 7<!--> <!-->mg/h, adrénaline 8<!--> <!-->mg/h, dobutamine, glucagon 6<!--> <!-->mg, insuline 30 UI, glucose 30 % 500<!--> <!-->mL, bicarbonate molaire 500<!--> <!-->mL, et gluconate de calcium 2<!--> <!-->g puis admise en réanimation cardiologique. À son arrivée, sa PA<!--> <!-->=<!--> <!-->90/50<!--> <!-->mm Hg, sa Fréquence cardiaque (FC)<!--> <!-->=<!--> <!-->60 bpm. Le traitement par adrénaline, noradrénaline, insuline-glucose, et glucagon est poursuivi. L’ECG montre un rythme d’échappement jonctionnel avec QRS fins à 50 bpm et un QTc à 569<!--> <!-->ms. L’échographie transthoracique est normale. À J2 à 10<!--> <!-->h, la patiente présente un choc cardiogénique réfractaire motivant l’implantation d’une ExtraCorporeal Membrane Oxygenation (ECMO) veino-artérielle fémoro-fémorale périphérique. Ont été réalisés des dosages plasmatiques de vérapamil (LC/QTOF) à J1 (0,53 mcg/mL), J3 (0,88 mcg/mL) J5 (2,9 mcg/mL) et J8 (2,6 mcg/mL) et de bisoprolol (LC MS/MS) à J1 (0,31 mcg/mL), J3 (0,13 mcg/mL), J5 (0,035 mcg/mL) et J8 (< 0,025 mcg/mL). Une endoscopie digestive haute (EDH) est réalisée à J5, en raison de l’élévation du dosage du vérapamil dans l’hypothèse d’un pharmacobézoard in fine non retrouvé. L’évolution est favorable. L’ECMO est sevrée à J11. La patiente sortira de réanimation dans les suites.</div></div><div><h3>Résultats</h3><div>Discussion : Le vérapamil est un inhibiteur calcique rapidement absorbé per os, les concentrations maximales de la forme à libération prolongée sont atteintes en 5<!--> <!-->h. Il est métabolisé dans le foie par les cytochromes, avec production de 12 métabolites, dont le norvérapamil actif. 70 % de la dose sont éliminés par le rein en 5<!--> <!-->jours. La concentration thérapeutique est de 2,10–5 à 2,5,10–4 mcg/mL, toxique à partir de 0,001 mcg/mL et les décès décrits à partir de cette dose. Le bisoprolol est un bétabloquant à forte affinité béta 1. Il est rapidement absorbé per os. 50 % sont métabolisés par le foie en métabolites inactifs, puis éliminés par les reins, les 50 % restants éliminés par le rein sous forme inchangée. La demi-vie d’élimination plasmatique est de 12<!--> <!-->h. La conc","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S49"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529017","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}
Sabrina Cherki , Yanis Schelpe , Thibaut Massot , Nicolas Ducourneau , Johan Thiery , Valérie Gibaja
{"title":"Substances psychoactives dans l’Est de la France : tendances récentes observées par le dispositif SINTES","authors":"Sabrina Cherki , Yanis Schelpe , Thibaut Massot , Nicolas Ducourneau , Johan Thiery , Valérie Gibaja","doi":"10.1016/j.toxac.2025.01.083","DOIUrl":"10.1016/j.toxac.2025.01.083","url":null,"abstract":"<div><h3>Objectifs</h3><div>Le système d’identification national des toxiques et substances (SINTES), mis en place par L’observatoire français des drogues et des tendances addictives (OFDT), permet d’analyser des produits collectés directement auprès d’usagers de drogues, notamment dans le cadre d’effets indésirables graves ressentis. Ce dispositif permet de connaître les compositions exactes de ces produits et de suivre l’évolution des substances psychoactives (SPA) circulant sur le territoire français. Les centres d’Addictovigilance, de leur côté, assurent la surveillance, l’évaluation et la prévention des risques des SPA à potentiel d’abus. Addictovigilance et SINTES interviennent donc en complémentarité pour informer des risques liés à la consommation des SPA.</div><div>Nous présentons un état des lieux des résultats d’analyse des collectes SINTES réalisées sur le territoire du centre d’Addictovigilance des régions Est de la France entre 2021 et 2023.</div></div><div><h3>Méthodes</h3><div>Il s’agit d’une étude observationnelle, rétrospective dont l’objectif principal est d’établir un état des lieux des SPA identifiées lors des analyses des collectes SINTES réalisées en Bourgogne Franche-Comté (BFC), Alsace et Grand-Est (GE) sur la période 2021–2023. Les objectifs secondaires sont : (1) d’évaluer les caractéristiques des collectes de produits, (2) de définir le profil démographique des usagers, (3) d’identifier la typologie des substances retrouvées dans les analyses. Une comparaison aux données nationales disponibles sera également réalisée.</div></div><div><h3>Résultats</h3><div>Un total de 236 collectes SINTES ont été réalisées en régions Est sur les 3 années d’étude. Celles-ci étaient en constante augmentation sur la période d’étude (89 collectes en 2023 vs 75 en 2022 et 72 en 2021). Les collectes proviennent majoritairement des régions GE (44,1 %) et Alsace (31,8 %) avec une proportion en GE en augmentation au fil du temps. Quelle que soit l’année, les collectes ont été réalisées dans la grande majorité suite à des effets indésirables (bénins ou graves) ou des effets inattendus ressentis par les usagers ((80 % en 2021, 78 % en 2022 et 65 % en 2023). À noter, la part des collectes de nouveaux produits a augmenté en 2023 (13 % vs 7 % en 2022 et 8 % en 2021).</div><div>Les usagers de SPA ayant cédé des échantillons de leurs produits étaient majoritairement des hommes (77 %), et 75 % des consommateurs n’avaient pas plus de 40<!--> <!-->ans quelle que soit l’année (âges extrêmes : 14–64<!--> <!-->ans). Nous notons cependant une grande dispersion de la distribution de l’âge, incluant des jeunes mineurs de moins de 15<!--> <!-->ans. La proportion de produits retrouvés conformes aux substances supposées composer les produits analysés est en moyenne de 69 % sur la période (vs 68 % au niveau national). Les substances retrouvées sont majoritairement des molécules anciennement connues : cocaïne, héroïne et THC en tête mais cependant en diminution en ","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S54"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528619","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}
Joelle Micallef , Tiphaine Raingeard , Elisabeth Jouve Jouve , Elisabeth Frauger , Nathalie Fouilhé
{"title":"Augmentation de l’usage de kétamine non pharmaceutique en France et de ses risques sanitaires : que nous apprennent les données du Réseau Français d’Addictovigilance ?","authors":"Joelle Micallef , Tiphaine Raingeard , Elisabeth Jouve Jouve , Elisabeth Frauger , Nathalie Fouilhé","doi":"10.1016/j.toxac.2025.01.081","DOIUrl":"10.1016/j.toxac.2025.01.081","url":null,"abstract":"<div><h3>Objectifs</h3><div>La kétamine fait l’objet d’une surveillance de son usage et de ses complications sanitaires par le réseau Français d’Addictovigilance. Un point récemment publié soulignait le virage pris en France avec ce produit cantonné surtout aux milieux techno [Gandolfo et al., 2024;38(5):978–987].</div><div>Dans ce contexte, nous présentons une synthèse des données sur l’usage détourné de kétamine de 2020 à 2023 (P2), afin de décrire l’évolution de cette consommation et de ses caractéristiques en France notamment par rapport aux années antérieurs (2017-2020)(P1).</div><div>Les P1 et P2 sont déterminées par les périodes de surveillance des rapports nationaux d’Addictovigilance, réalisées à la demande de l’ANSM (agence nationale de sécurité du médicament et des produits de santé).</div></div><div><h3>Méthodes</h3><div>Une analyse de données multi-sources a été effectuée : -Analyse des cas d’addictovigilance : cas/notS (grave et non grave) des CEIP-A.</div><div>Analyse des outils spécifiques de pharmacosurveillance : 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), DRAMES (décès en relation avec l’abus de médicaments et de substances via une collaboration avec les toxicologues analystes).</div></div><div><h3>Résultats</h3><div>(227/372), soit une multiplication d’un facteur 2 (157 sur P1). La moyenne d’âge est de 25,8<!--> <!-->ans (8,3 % de mineurs), surtout des hommes (67,5 %). La fréquence de prise de la kétamine y est régulière (39 % quotidienne, 50 % hebdomadaire). Cet usage se fait dans un contexte festif/récréatif (55 %), « auto-thérapeutique » (37,5 %) et de chemsex (7,5 %). Ces 372 observations sont caractérisées par 399 effets/troubles : 27 % des troubles psychiatriques, 21 % des troubles du SNC, 18 % des troubles de l’usage, 12 % des troubles gastro-hépatiques, 8 % des troubles urinaires.</div><div>Les 2 catégories qui ont le plus augmenté (P2 versus P1) sont les troubles urinaires (passés de 3 % à 8 %) et les troubles de l’usage (passés de 10 % à 18 %). Ces troubles urinaires sont des cystites interstitielles diagnostiquées comme telle et des symptômes évocateurs de ces cystites (dysurie, hématurie, pollakiurie…). Des thérapeutiques chirurgicales sont mentionnées pour 3 d’entre elles (hydrodistension, cystectomie). Parmi les 18 % de troubles de l’usage (<em>n</em> <!-->=<!--> <!-->72), il y en a 20 qui sont en demande de sevrage à la kétamine, 5 qui présente un craving. Deux situations sont rapportées dans ce cadre, décrivant des usagers/patients se rendant à l’hôpital (via les services d’Urgence) afin d’obtenir de la kétamine pharmaceutique. Sur les données DRAMES, il y a 8 cas où la kétamine est reconnue responsable du décès (seule ou en association) contre 3 dans le précédent rapport. Sur les données OPPIDUM, le nombre d’usage","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S53"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528707","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}
Nicolas Fabresse , Gnominding Bayo , Anne-Laure Pelissier Alicot , Marie Carles , Caroline Solas Chesneau
{"title":"Optimization and validation of a Dried Blood Spot (DBS) method for high-resolution mass spectrometry in forensic toxicology","authors":"Nicolas Fabresse , Gnominding Bayo , Anne-Laure Pelissier Alicot , Marie Carles , Caroline Solas Chesneau","doi":"10.1016/j.toxac.2025.01.032","DOIUrl":"10.1016/j.toxac.2025.01.032","url":null,"abstract":"<div><h3>Aim</h3><div>This study aimed to optimize, validate, and apply a toxicological screening method using Dried Blood Spot (DBS) coupled with high-resolution mass spectrometry (HRMS) in forensic toxicology. The primary goals included method refinement for extraction and analysis, validation based on critical performance parameters, and testing the method with post-mortem blood samples.</div></div><div><h3>Method</h3><div>Samples containing 20 xenobiotics from diverse pharmacological classes were prepared for DBS analysis. Targeted and non-targeted toxicological screening was performed by LC-HRMS (Orbitrap Exploris 120, ThermoFisher Scientific). Optimization included the extraction process (sonication time, recovery volume) and analytical parameters (injection volume, ion intensity thresholds for data dependent analysis). Validation followed European Medicines Agency (EMA) guidelines, assessing repeatability, reproducibility, stability, linearity, matrix effect, extraction yield, and lower limits of quantification (LLOQ). The limit of identification (LOI) was also evaluated with 135 compounds. Post-mortem blood samples (<em>n</em> <!-->=<!--> <!-->20) were analyzed to compare the method's accuracy and sensitivity with the laboratory's standard LC-HRMS procedure.</div></div><div><h3>Results</h3><div>Optimization yielded a final DBS method with a recovery volume of 70<!--> <!-->μL, 30-minute sonication, and a 25<!--> <!-->μL injection volume. Validation demonstrated reproducibility, linearity, and acceptable LLOQ for most compounds, while some issues arose with stability at room temperature (mephedrone and 6-acetylmorphine) and matrix effect (ketamine). Extraction yields were low overall (15–85%), but sensitivity was sufficient for the detection of therapeutic concentrations (mean LOI of 48<!--> <!-->ng/mL for 135 compounds). Comparative analysis with LC–HRMS showed similar identification results (65 compounds), except for three discrepancies (bisoprolol (6<!--> <!-->ng/mL), codeine (<<!--> <!-->5<!--> <!-->ng/mL) and oxazepam (5<!--> <!-->ng/mL) were not detected using DBS) confirming the DBS method's detection capability.</div></div><div><h3>Conclusion</h3><div>The DBS method effectively balances small sample volumes and analytical robustness, presenting a reproducible, linear, and sensitive alternative for toxicological screenings. While unsuitable for precise quantification in forensic settings, DBS offers potential for qualitative analyses and broader toxicological applications. Further validations, including inter-sample contamination and extended compound library integration, should be done to make this method suitable for routine analysis of post-mortem blood samples.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S24"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528816","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":"Fatal intoxication of 1-Thiophen-2-yl-2-MethylAminoPropane(-2-MPA): Forensic case report","authors":"Libargachew Mihretu, Dr Karangwa Charles","doi":"10.1016/j.toxac.2025.01.070","DOIUrl":"10.1016/j.toxac.2025.01.070","url":null,"abstract":"<div><h3>Aim</h3><div>To identify whether 2-MPA was the cause of the death or not.</div></div><div><h3>Case</h3><div>A 27-year-old man who had drunk several large pints and had used some novel psychoactive substances (NPS) was found unconsciousness early in the morning in his room with some plastic packets, where two of them were opened and one sealed contained white tablets (jumping beans). The tablets were found adjacent to the dead body. He was brought to a Kaciyru hospital (Kigali, Rwanda); at the hospital, he was found to be unresponsive with no mental state and a lack of coordination. The autopsy was conducted as per the request from the Rwanda Investigation Bureau (RIB) and the findings revealed that there were no marks; the body did not show any decomposition and both the internal and external examinations showed no evidence of injury. The brain appeared congested and edematous; kidneys, lungs, and liver appeared congested, and the heart appeared normal. 10<!--> <!-->mL of blood sample was collected directly from the heart. The postmortem report indicated sudden cardiac death through cardiac dysrhythmia, but there was no medical history of previous heart disease.</div></div><div><h3>Method</h3><div>The cardiac blood sample and the packets of jumping beans were collected and analysis was carried out for drug intoxication. Physical examination of the drug was performed using the microscopic technique; The Fourier Transform Infrared (FTIR) spectrometer was used as confirmatory analysis. The proton nuclear magnetic resonance 1H-NMR was used to record the proton NMR of the target compound. NPS from post-mortem cardiac blood samples was analyzed by SPE-GC-MS after appropriate sample pretreatment procedures.</div></div><div><h3>Results</h3><div>The finding suggested the presence of methiopropamine (2-MPA) in the suspected seized drug. Moreover, the structural isomer of 2-MPA was detected and the concentration of 2-MPA in the decedent's blood was 752<!--> <!-->±<!--> <!-->26 ng/mL.</div></div><div><h3>Conclusion</h3><div>The preliminary presumptive blood test revealed that the suspected drug gave a positive result with GC-MS analysis. Besides, the FTIR and NMR confirmed that the suspected drug was 2-MPA. The quantitative determination of MPA was also performed using GC-MS and the result showed that a high concentration of MPA was reported as acute toxicity was obtained in the cardiac blood. Thus, the cause of death was certified as acute 2-MPA intoxication.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S46"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528833","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}
Anne Batisse , Céline Eiden , Clémence Lacroix , Joelle Micallef , Nathalie Fouilhe , Fan Le Réseau Des Centres D’Addictovigilance
{"title":"NPS : données actualisées des dispositifs d’addictovigilance","authors":"Anne Batisse , Céline Eiden , Clémence Lacroix , Joelle Micallef , Nathalie Fouilhe , Fan Le Réseau Des Centres D’Addictovigilance","doi":"10.1016/j.toxac.2025.01.078","DOIUrl":"10.1016/j.toxac.2025.01.078","url":null,"abstract":"<div><h3>Objectifs</h3><div>La connaissance des « nouvelles drogues de synthèse » (NPS) passe par les nécessaires étapes de détection, documentation, surveillance et synthèse afin de prévenir au mieux les risques sur le terrain et d’établir des prévisions. En France, ces molécules sont surveillées par le réseau d’addictovigilance et une première évaluation réalisée en 2020 avait montré une diffusion des NPS à la fois pour mimer les drogues illicites, mais aussi comme drogues mimant les médicaments psychoactifs [Batisse A, et al. Neurotoxicology. 2020; 79:20–24]. L’objectif est la mise à jour des données d’addictovigilance concernant les NPS.</div></div><div><h3>Méthodes</h3><div>Extraction et analyse des données issues des centres d’addictovigilance à travers les outils pharmacoépidémiologiques suivants : Notifications spontanées (NotS), OPPIDUM, DRAMES.</div></div><div><h3>Results</h3><div>Une augmentation du nombre de NotS est observée avec un nombre de cas de complications en lien avec les NPS qui double en 4<!--> <!-->ans (2020–2023), pour atteindre 604 cas en 2023. Comme chaque année, le top 3 des familles de substances se partage entre les cathinones de synthèse (1), les cannabinoïdes de synthèse (2) et les dissociatifs (3). À partir de 2023, la famille des cannabinoïdes prend de plus en plus d’importance avec l’arrivée des dérivés d’hémisynthèse (HHC, THCP...). La problématique des cannabinoïdes est multiforme puisque ceux-ci se retrouvent à la fois dans les E-liquides, comme produits de coupe des drogues illicites (cannabis, héroïne) ou comme substance endémique (la chimique dans l’océan indien), tandis que l’usage des cathinones de synthèse semble se diffuser en dehors de la pratique du chemsex. Dans le programme OPPIDUM, 431 sujets ont été inclus sur 8<!--> <!-->ans (2016 à 2023). On observe une augmentation des usagers consommateurs de NPS passant de 17 (0,3 %) sujets en 2016 à 92 (1,7 %) en 2023. Les usagers sont majoritairement des hommes (92,5 %), d’âge médian 36<!--> <!-->ans [28-44], polyconsommateurs dans 76,3 % des cas. 83 % des usagers de NPS déclarent consommer des cathinones et pour 10 % d’entre eux la 3-MMC était le premier produit illicite consommé (vs 3 % au niveau national). Pour 37 % d’entre eux, c’est la famille NPS-cathinone qui les a rendus dépendants (principalement la 3-MMC). L’usage est décrit par voie IV pour 51 % (vs 9 %), nasale 54 % (vs 26 %). Une dépendance alcoolique est associée dans 18,5 % (vs 30 %) et les sujets déclarent une substitution aux opioïdes dans 16 % des cas (vs 66 %). Dans le programme DRAMES, 108 décès (134 NPS mentionnées) ont été inclus sur 10<!--> <!-->ans (2012 à 2022). On observe une augmentation des décès d’usagers de NPS passant de 3 cas en 2012 vs 14 en 2022. Les usagers sont majoritairement des hommes (95 %), d’âge médian 38<!--> <!-->ans [32-50] avec une surreprésentation des NPS stimulants (81 % des décès NPS (88/108).</div></div><div><h3>Conclusion</h3><div>Plusieurs phénomènes mar","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S51"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528869","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":"The use of artificial intelligence in forensic toxicology","authors":"Simon Elliott , Sarah MR Wille","doi":"10.1016/j.toxac.2025.01.013","DOIUrl":"10.1016/j.toxac.2025.01.013","url":null,"abstract":"<div><h3>Objectives</h3><div>The integration of artificial intelligence (AI) into forensic toxicology has the potential to revolutionize this domain by enhancing efficiency, and interpretability of toxicological analyses. AI technologies, including machine learning (ML), deep learning, generative AI and expert systems offer advanced data analysis capabilities that can significantly improve the way forensic toxicologists will work in the future. These systems can enhance efficiency by automating time-intensive laboratory processes, offering significant advancements in the detection of compounds, and processing of data, whilst reducing human error. Techniques such as natural language processing (NLP) are employed to extract relevant information from scientific literature, enhancing the knowledge base available to forensic toxicologists. Other AI models are trained on extensive datasets comprising chemical structures, toxicological outcomes, and biological assay results, to finally predict the toxicity of new compounds, automate the identification of substances in biological samples, and assist in the interpretation of complex toxicological data.</div></div><div><h3>Methods</h3><div>The opportunities and challenges associated with implementing the different AI technologies in forensic toxicology, with a focus on generative AI, expert systems, and ML will be reviewed. In addition, a summary of the aims and tasks of ‘The International Association of Forensic Toxicologists’ (TIAFT) Task Force concerning AI will be discussed.</div></div><div><h3>Results</h3><div>This summary provides a review of the current integration of AI into forensic toxicology, highlighting its potential to revolutionize the field by increasing efficiency, enhancing interpretability, and supporting forensic investigations. Key findings include (a) the potential of NLP and generative AI to automate literature reviews and report generation, (b) use of expert systems for rapid drug identification in biological samples, and (c) ML models for interpreting complex toxicological data, such as drug interactions and biomarker detection.</div></div><div><h3>Discussion</h3><div>Despite the clear benefits of AI, the integration of AI in forensic toxicology faces several challenges. These include ensuring data quality and accessibility, addressing ethical concerns related to data privacy and algorithmic bias, and achieving regulatory acceptance of AI-driven methodologies. Transparent and explainable AI models are crucial for gaining trust within the forensic community and ensuring responsible use of technology.</div></div><div><h3>Conclusion</h3><div>The incorporation of AI into forensic toxicology holds promise for enhancing the accuracy, efficiency, and reliability of toxicological analyses. By leveraging AI technologies, forensic toxicologists can improve their ability to detect and interpret toxic substances, ultimately contributing to more effective forensic investigations and public safe","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S14"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528917","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":"Glucagon like peptide-1 analogues analysis in whole blood samples by the use of LC-ESI-HRMS method","authors":"Nadia Arbouche , Alice Ameline , Laurie Gheddar , Jean-Sébastien Raul , Pascal Kintz","doi":"10.1016/j.toxac.2024.11.005","DOIUrl":"10.1016/j.toxac.2024.11.005","url":null,"abstract":"<div><h3>Objective</h3><div>The use of GLP-1 analogues has been increasing worldwide in recent years due to their benefits in treating type II diabetes. Thanks to their effects on appetite regulation, in many countries they are also used, especially semaglutide, to treat obesity. However, due to their promotion by social media and celebrities as a weight-loss treatment, GLP-1 analogues are misused by a non-diabetic and non-obese population and also by a young public, which is the main target of these media. Following the alert by the ANSM (Agence nationale de sécurité du médicament) in France and the FDA (Food and Drug Administration) in the United States, which imposed the addition of fatal effects to the list of side effects for semaglutide, the misuse seems to become a public health problem. For this reason, it seems important that a toxicology laboratory is able to evidence the presence of these drugs in blood. In this study, the authors have developed and validated a method for the identification and quantification of semaglutide and liraglutide in whole blood using a LC-HRMS method.</div></div><div><h3>Methods</h3><div>LC separation was achieved using a Waters Acquity HSS C18 column (150<!--> <!-->×<!--> <!-->2.1<!--> <!-->×<!--> <!-->1.8<!--> <!-->μm) with a controlled temperature maintained at 50<!--> <!-->°C. A 5-μL injection with a 0.25<!--> <!-->mL/min flow of waters with 0.1% of formic acid (solvent A) and acetonitrile with 0.1% of formic acid (solvent B) was used. A Xevo G2-XS Q-TOF high-resolution mass spectrometer (Waters corporation, Milford, MA, USA) was used, operating in positive ion mode and in sensitivity mode. In MS scanning, data were acquired from 500 to 2000<!--> <!-->m/z. For semaglutide, the 4-fold charged [M<!--> <!-->+<!--> <!-->4H]<sup>4+</sup> molecule was observed at m/z 1029.29752 (which deconvolutes to 4117.70139), while for liraglutide the 4-fold charged ion [M<!--> <!-->+<!--> <!-->4H]<sup>4+</sup> was observed at 938.76490 (which deconvolutes to 3754.53707).</div><div>The extraction was performed by blood protein precipitation using a mix of ACN/MeOH (70:30), after the addition of 50<!--> <!-->ng/mL of internal standard (bovin insulin). The method was applied to authentic whole blood samples following a hospital request for GLP-1 analogs determination and to postmortem blood samples. The blood samples were stored at<!--> <!-->+<!--> <!-->4<!--> <!-->°C until analysis.</div></div><div><h3>Results and discussion</h3><div>Usual therapeutic blood concentrations of both drugs are in the range 50-150<!--> <!-->ng/mL. The validation procedure demonstrated an acceptable linearity between 2 and 500<!--> <!-->ng/mL. LOD and LOQ were 1 and 2<!--> <!-->ng/mL, respectively. Intra and inter-day precision were below 20% at three concentrations. The method was successfully applied to the blood samples of 3 diabetic patients under treatment of semaglutide (concentrations ranged from 31 to 70<!--> <!-->ng/mL) and to one postmor","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S61"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529299","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}
Florian Hakim , Caroline Ghoul , Hugo Girard , Quentin Scanvion , Yann Delannoy , Jean-François Wiart , Luc Humbert , Delphine Allorge , Valéry Hédouin , Jean-Michel Gaulier , Alexandr Gish , Myriam Bertrand N. Doye , Camille Richeval
{"title":"Main results of the IN CADAVER protocol: The value of using dried blood spots (DBS) in post-mortem forensic toxicology","authors":"Florian Hakim , Caroline Ghoul , Hugo Girard , Quentin Scanvion , Yann Delannoy , Jean-François Wiart , Luc Humbert , Delphine Allorge , Valéry Hédouin , Jean-Michel Gaulier , Alexandr Gish , Myriam Bertrand N. Doye , Camille Richeval","doi":"10.1016/j.toxac.2025.01.030","DOIUrl":"10.1016/j.toxac.2025.01.030","url":null,"abstract":"<div><h3>Aim</h3><div>In recent years, post-mortem analytical toxicology has undergone significant technical advances (pre-analytical extraction stage and analytical instruments), improving analysis performance. However, two challenges remain unchanged: (1) biological samples, usually autopsy samples, of several milliliters in size, constituting time-consuming and costly pre- and post-analytical management seals, and (2) difficulties in interpretation due to in cadaver phenomena during the post-mortem period (degradation and PMR), in vitro instability, and imperfections of reference systems for interpretation. In addition, in our experience, toxicological analysis as part of the search for the cause of death can be carried out correctly 9 out of 10 cases using post-mortem blood analysis alone. To overcome the two challenges mentioned above, the IN CADAVER protocol explores the possibility of carrying out such tasks using 70<!--> <!-->μL of capillary blood collected at the time of foreign body removal. With the agreement of the judicial authorities, this single-center protocol aims to compare the toxicological results obtained (1) in micro-samples versus conventional samples taken during autopsy (T2), and (2) in micro-samples taken during body removal (T1) versus autopsy ones (T2). Here are the main results.</div></div><div><h3>Method</h3><div>The blood micro-samples consist of 2 DBS of 10<!--> <!-->μL (VAMS Mitra Neoteryx) and 50<!--> <!-->μL on a fluorinated microtube dedicated to capillary blood sampling. These micro-samples are taken (capillary vein of the foot or femoral artery) at T1 and T2, and are only analyzed when toxicological analyses are required. All samples were analyzed using the same methods (LC-HRMS, LC-MS/MS and HS-CG-FID), with additional assays for alcohol biomarkers (PEth and EtG) in the micro-samples. Only cases with positive toxicological results are finally included in the IN CADAVER protocol.</div></div><div><h3>Results</h3><div>Seventy-two cases of death were sampled, 35 of which were requisitioned for toxicological analysis: 33 revealed the presence of xenobiotics (mean age 41 years-old; sex-ratio 3.4; 45<!--> <!-->hours as mean time between T1 and T2).</div><div>At T2, all the molecules detected in the autopsy blood samples were also detected in the micro-samples, and the differences between the concentrations measured in the autopsy blood samples and the autopsy micro-samples do not affect the interpretation. There was no significant difference between the blood concentrations of ethanol, PEth and ETG measured at T1 and T2. With regard to opiates, the main finding was that in 2 out of 3 cases, 6-MAM was only detected (at T1 and T2) in DBS. Certain opioids such as tramadol (and N-desmethyltramadol) showed an increasing trend between T1 and T2 (suggesting PMR). THC and related metabolites were detected in all 3 blood samples, but the concentrations measured in DBS were lower (probably due to the extraction difficulty fr","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S23"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528827","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}