Toxicologie Analytique et Clinique最新文献

{"title":"Is it possible to test for GHB in hair after a single administration?","authors":"Francesco Paolo Busardò","doi":"10.1016/j.toxac.2025.01.056","DOIUrl":"10.1016/j.toxac.2025.01.056","url":null,"abstract":"<div><h3>Objective</h3><div>Improving analytical determination of GHB in hair after a single administration through the assessment of promising biomarkers to distinguish between endogenous and exogenous GHB values.</div></div><div><h3>Introduction</h3><div>Gamma-hydroxybutyrate (GHB) is a compound with both therapeutic and illicit uses, often involved in cases of drug-facilitated crimes. Due to its rapid metabolism and endogenous production, its detection in hair after a single exposure, is critical, particularly in ambiguous cases where the ratio between endogenous and exogenous value is unclear.</div></div><div><h3>Methods</h3><div>Conventional GHB methods often fail to provide clear evidence of exogenous GHB consumption, particularly in cases of single or low-dose administration. Hyphenated analytical techniques supported by the detection of new biomarkers of consumption, such as GABA, provide useful support in interpreting GHB endogenous and exogenous values and represent a useful strategy to clarify exogenous GHB consumption.</div></div><div><h3>Results</h3><div>Differentiation between endogenous and exogenous GHB values remains challenging, however, the application of specific biomarkers such as GHB-glucuronide and GABA could potentially provide useful support.</div><div>The presence of one or more specific biomarkers reinforces traditional analysis (segmental hair analysis of GHB and determination of a ratio).</div><div>These results underline the importance of new potential biomarkers of consumption in improving the reliability and specificity of GHB analysis in hair.</div></div><div><h3>Discussion</h3><div>The relationship between endogenous and exogenous GHB values is a critical task in forensic toxicology, especially in cases where results are ambiguous. Biomarkers, such as GABA, offer additional data which can be useful in demonstrating exogenous GHB consumption.</div><div>As a product of GHB metabolism, the inclusion of GABA as a biomarker could integrate existing methods and biomarkers, offering a more comprehensive analytical profile for accurately determining and clarifying GHB exposure.</div></div><div><h3>Conclusion</h3><div>The determination of a single GHB administration in hair is a very difficult task. The inclusion of promising biomarkers, such as GABA, may represent a valid support for a correct interpretation of each case.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S38"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528828","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":"LC-DAD: A tool from the past to identify isomers of new psychoactives substances. Application to chloromethcathinones","authors":"Pauline Baradian ,&nbsp;Camille Chatenay ,&nbsp;Guillaume Hoizey ,&nbsp;Laurent Fanton ,&nbsp;Charline Bottinelli","doi":"10.1016/j.toxac.2025.01.068","DOIUrl":"10.1016/j.toxac.2025.01.068","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Aim&lt;/h3&gt;&lt;div&gt;To formally identify the isomers of chloromethcathinone (x-CMC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;General toxicological unknown screening performed on peripheral blood of a man found dead at home in a context of chemsex revealed x-CMC on gas chromatography (GC) coupled with mass spectrometry (MS) using the Cayman commercial library. To formally identify the isomer, commercial standards of 3-CMC and 4-CMC were obtained and integrated in homemade spectrum libraries (mass and UV) by analyzing them using screening methods: GC-MS (after acetylation) and liquid chromatography (LC) coupled to diode array detection incremented to a mass spectrometer (DAD/MS), plus targeted methods dedicated to new psychoactive substances (NPSs) by tandem mass spectrometry: GC-MS/MS and LC-MS/MS. These methods are in daily use in laboratories in forensic contexts (determination of cause of death, drug abuse). Apolar columns were used for all methods. The conditions of the various methods have been previously published (Bottinelli, Toxac, 2017,29,123–129; Epain, Int Legal Med, 2024, 138, 1813–1820).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Whatever the MS method and whether the compound was acetylated or not (GC), an identical spectrum was observed for 3-CMC and 4-CMC. The specific m/z ions selected for GC-MS were 111, 139 and 239. For GC-MS/MS, the transitions were 138.9&lt;!--&gt; &lt;!--&gt;&gt;&lt;!--&gt; &lt;!--&gt;110.9, 138.9&lt;!--&gt; &lt;!--&gt;&gt;&lt;!--&gt; &lt;!--&gt;75.0 and 112.9&lt;!--&gt; &lt;!--&gt;&gt;&lt;!--&gt; &lt;!--&gt;75.0, and for LC-MS/MS 197.9&lt;!--&gt; &lt;!--&gt;&gt;&lt;!--&gt; &lt;!--&gt;145.0 and 197.9&lt;!--&gt; &lt;!--&gt;&gt;&lt;!--&gt; &lt;!--&gt;180.0. Under the chromatographic conditions tested, an identical retention time (RT) was observed for the two isomers using GC-MS and GC-MS/MS, making them completely indistinguishable, despite many temperature gradient tests. However, the LC methods obtained distinct RTs: 3.73&lt;!--&gt; &lt;!--&gt;min and 3.52&lt;!--&gt; &lt;!--&gt;min for 3-CMC and 4-CMC, respectively, on LC-MS/MS. As well as being discriminated by RT, 3-CMC (6.32&lt;!--&gt; &lt;!--&gt;min) and 4-CMC (6.54&lt;!--&gt; &lt;!--&gt;min) were clearly distinguishable on LC-DAD/MS by their absorption spectra. Absorbance maxima were observed at wavelengths of 210 and 250&lt;!--&gt; &lt;!--&gt;nm for 3-CMC and 197 and 262&lt;!--&gt; &lt;!--&gt;nm for 4-CMC. Concerning isomer identification in the postmortem case described here, 3-CMC was formally identified by LC-DAD/MS and then quantified (33.7 ng/mL) in the peripheral blood by LC-MS/MS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In some cases, it is difficult to distinguish NPS isomers. It is generally expected that compounds with similar structures will react similarly under given analytic conditions. Therefore, it was initially suspected that the x-CMC isomers would behave identically to the x-MMC isomers: i.e., differentiable by RT on GC and undistinguishable on LC-MS/MS. The difference in these structures lies in the presence of a chlorine atom (CMC) replacing a methyl group (MMC). On LC, a chloride group allows additional interaction with the sta","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S45"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528832","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":"Machine learning in forensic toxicology: Applications, experiences, and future directions","authors":"Michael Scholz","doi":"10.1016/j.toxac.2025.01.014","DOIUrl":"10.1016/j.toxac.2025.01.014","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Giving a basic overview of principles of machine learning and its pitfalls together with real world successful examples. This should help improve technological literacy of machine learning within the forensic toxicologist community.&lt;/div&gt;&lt;div&gt;The demands on a forensic toxicologist are changing rapidly. In the past, it was sufficient to operate a GC-MS or LC-MS device with often extremely user-unfriendly software to obtain a result. Then the evaluation of a case could begin. However, as analytical instruments have become faster, more sensitive, versatile and powerful, forensic toxicology has evolved in parallel. This development has been accompanied by a rapid increase in the volume of data. This trend is particularly evident in high-resolution mass spectrometry and non-targeted search analysis, in which a large number of substances can be detected in complex biological samples. Forensic toxicologists are no longer interested only in prescription or illegal drugs, but in the totality of all small molecules in the human body (the so-called metabolome). Under certain circumstances, changes in the metabolome can provide clues to drug use, cause of death, drunk or even drowsy driving. It is obvious that these huge amounts of data can no longer be analyzed manually.&lt;/div&gt;&lt;div&gt;Machine learning (ML), a subfield of artificial intelligence, has proven to be extremely powerful and promising in tackling large, complex, and high-dimensional data sets. ML can make predictions, find patterns, or classify data. The three-machine learning types are supervised, unsupervised, and reinforcement learning. It has emerged over the last decade, and consists of many different learning algorithms (e.g. Linear Regression, Logistic Regression, Decision Trees, Random Forest, Support Vector Machines, Naive Bayes and others). Currently, these algorithms are finding their way into forensic toxicology. However, this transformative technology is not without its challenges. While the underlying principles of ML are easy to understand, there are a lot of pitfalls to avoid ensuring that ML can actually improve results in forensic toxicology. There are so many easy-to-make mistakes that can cause an ML model to appear to perform well, when in reality it does not.&lt;/div&gt;&lt;div&gt;The most common pitfalls are: inadequate or non-representative training data, poor quality of data or overfitting and underfitting. It is of the utmost importance to correctly split datasets, train algorithms, and validate results. Another problem that severely impacts machine-learning algorithms is the curse of dimensionality, a phenomenon where the efficiency and effectiveness of algorithms deteriorate as the dimensionality of the data increases exponentially. Consequently, the skilled forensic toxicologist must employ dimensionality reduction techniques such as selection of the most relevant features from the original dataset while discarding irrelevant or redundant ones (feature selection). This reduc","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages S14-S15"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528918","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 accidents at high altitude and cannabis use: A 10-year retrospective study in the French Alps","authors":"Coralie Boudin ,&nbsp;Hélène Eysseric-Guerin ,&nbsp;François Paysant ,&nbsp;Françoise Stanke-Labesque ,&nbsp;Virginie Scolan ,&nbsp;Théo Willeman","doi":"10.1016/j.toxac.2025.01.025","DOIUrl":"10.1016/j.toxac.2025.01.025","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Aim&lt;/h3&gt;&lt;div&gt;Mountains and high altitudes in general are environments with a high accident and fatality rate. In these areas, oxygen availability is reduced, air is thinner, temperatures are colder, and UV levels are increased. In France, the use of illicit drugs (other than cannabis) was 1.8% in 2014 and has risen to 3.9% in 2023. The most widely used drug is cannabis, with a prevalence of use of 10.8% in 2023 and stable over the last ten years according to OFDT. The aim of this study is therefore to assess the prevalence of narcotics and psychoactive drugs in fatal accidents in the French Alps.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;This retrospective study concerns 10 years of forensic autopsies with reference toxicological expertise, following fatal accidents occurring in the French Alps between 2014 and 2023. The data collected includes accidents involving downhill skiing (on- and off-piste), ski touring, snowboarding, paragliding, wingsuiting, aeroplanes, helicopters, gliders, hiking, snowshoeing, canyoning, kayaking, climbing, mountaineering, running, mountain biking, cycling and parties at altitude.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Between 2014 and 2023, a total of 121 people in the Alps died in accidents at altitude (99 men and 22 women, aged between 10 and 86, with an average age of 43). None of these cases involved narcotics other than cannabis or significant psychoactive drugs. Nine cases involved cannabis, 9 men aged between 17 and 49, with an average age of 28. One case occurred in 2015, 3 in 2016, 3 in 2022 and 2 in 2023. The influence of this narcotic was not considered for 3 of the 9 cases because only urine or bile samples were positive. The other 6 cases had blood THC concentrations ranging from 0.53 to 4.6&lt;!--&gt; &lt;!--&gt;ng/mL, THC-OH concentrations, when this metabolite was identified, ranging from 0.7 to 1.9&lt;!--&gt; &lt;!--&gt;ng/mL, and THC-COOH concentrations ranging from 3.1 to 24.2&lt;!--&gt; &lt;!--&gt;ng/mL. Of these 6 cases, 3 deaths were the result of accidents while downhill on-piste skiing, off-piste skiing and ski touring, 1 canyoning accident, 1 aircraft pilot accident and 1 accident during a party at altitude.&lt;/div&gt;&lt;div&gt;Finally, over 10 years, 5.0% of people who died in these accidents at high altitude were under the influence of a narcotic, and cannabis accounted for 100% of these cases. These results are to be compared with those obtained in the national DRAMES survey, which describes the prevalence of cannabis in indirect deaths as ranging from 50 to 78% between 2014 and 2022, with an average of 63% over 9 years (addictovigilance.fr). Another study carried out in 2016 among clients of two Mont Blanc refuges describes a prevalence of narcotics of 2.2 and 3.3% and more particularly cannabis of 4.6 and 2.6% &lt;span&gt;&lt;span&gt;[1]&lt;/span&gt;&lt;/span&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This retrospective study over 10 years shows that cannabis is the only narcotic found in fatal accidents at high altitude, constituting an additional ris","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages S20-S21"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528927","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":"Développement et application d’une approche de métabolomique pour l’identification de biomarqueurs précoces de toxicité du tabac, de la cigarette électronique et du tabac chauffé","authors":"Marie Lenski ,&nbsp;Sébastien Anthérieu ,&nbsp;Delphine Allorge","doi":"10.1016/j.toxac.2025.01.006","DOIUrl":"10.1016/j.toxac.2025.01.006","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objectif&lt;/h3&gt;&lt;div&gt;Le tabagisme est un facteur de risque établi pour diverses pathologies, dont le cancer du poumon. La cigarette électronique et le tabac chauffé sont de nouveaux produits arrivés sur le marché depuis quelques années et utilisés parfois comme aide au sevrage tabagique. Pourtant l’innocuité de ces produits n’est pas établie actuellement, du fait d’un manque d’études toxicologiques approfondies. Ces travaux visent à explorer et à comparer le métabolome de cellules pulmonaires humaines exposées à des émissions de cigarette électronique, de tabac chauffé ou de cigarettes de tabac, afin de mettre en évidence leurs empreintes métaboliques spécifiques et de potentiels biomarqueurs précoces de toxicité.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Méthodes&lt;/h3&gt;&lt;div&gt;Les méthodes de chromatographie liquide et de spectrométrie de masse haute résolution ont été développées et optimisées à partir de standards de métabolites. L’utilisation d’outils de &lt;em&gt;machine learning&lt;/em&gt; a permis de mettre en place une base de données de référence d’environ 114 000 métabolites, facilitant l’analyse des données de métabolomique non ciblée. Cette approche non ciblée a été utilisée pour analyser le métabolome de cellules épithéliales pulmonaires humaines immortalisées (BEAS-2B) cultivées à l’interface air-liquide et exposées à de l’air stérile (contrôle) ou aux émissions d’une cigarette de référence 3R4F (1 ou 2&lt;!--&gt; &lt;!--&gt;min), de tabac chauffé (30 ou 60&lt;!--&gt; &lt;!--&gt;min), ou de cigarette électronique (30 ou 60&lt;!--&gt; &lt;!--&gt;min) en utilisant la machine à fumer Vitrocell. Les durées d’exposition ont été choisies sur la base de doses sub-toxiques comparables (&gt; 80 % de viabilité cellulaire) précédemment rapportées, afin d’évaluer un effet potentiel dépendant du temps.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Résultats&lt;/h3&gt;&lt;div&gt;L’analyse chimiométrique des données de métabolomique a permis de souligner que les émissions de 3R4F et de tabac chauffé ont affecté de manière significative le métabolome par rapport aux contrôles, alors qu’aucune différence n’a été observée après les expositions à la cigarette électronique. La signature métabolomique mise en évidence à la suite de l’exposition aux produits du tabac était constituée de composés exogènes, dont l’un est cancérogène, ainsi que de métabolites endogènes, marqueurs d’effets. L’analyse des voies métaboliques dérégulées signe des altérations de diverses voies métaboliques et notamment le stress oxydant, le métabolisme énergétique et le métabolisme des lipides.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;Cette stratégie métabolomique offre de nouvelles perspectives pour une meilleure compréhension des variations du métabolisme cellulaire après une exposition à la cigarette ou au tabac chauffé, deux produits du tabac. Globalement, ces analyses in vitro suggèrent une toxicité moindre des aérosols de cigarette électronique par rapport à celle des émissions de la cigarette 3R4F et du tabac chauffé dans la lignée cellulaire BEAS-2B. Les métabolites dérégulés ","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages S10-S11"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529226","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":"Death by intoxication involving various new psychoactive substances including bromazolam","authors":"Maxime Alexandre ,&nbsp;Romain Pelletier ,&nbsp;Brendan Le Dare ,&nbsp;Isabelle Morel ,&nbsp;Renaud Bouvet ,&nbsp;Thomas Gicquel","doi":"10.1016/j.toxac.2025.01.029","DOIUrl":"10.1016/j.toxac.2025.01.029","url":null,"abstract":"<div><h3>Aim</h3><div>Benzodiazepines are frequently involved in deaths with toxicological components. In recent years, synthetic designer benzodiazepines (DBZD) have emerged, leading to new consumption patterns. Identifying these poorly documented molecules is essential in toxicologically induced death cases. We report here the case of a Caucasian 42-year-old woman who died in a context of NPS poly-consumption. Ten packets labeled as Research Chemicals were found near the body. Three packets, identified as containing Bromazolam and 2-MMC, were empty. Seven others, labeled as containing 4F-MPH, 4-FMA, 2-MMC, and O-DSMT, held tablets of various shapes and colors. A forensic body examination was conducted in order to collect blood sample. We performed a blood sample collection from the right subclavian artery. The tablets and post-mortem blood samples were collected and analyzed. The aim of the study is to report concentration levels in a fatality involving various new psychoactive substances (NPS), including Bromazolam and 2-MMC.</div></div><div><h3>Method</h3><div>Blood sample (200<!--> <!-->μL) was extracted with 300<!--> <!-->μL of zinc sulfate solution at 0.1<!--> <!-->M and additional 500<!--> <!-->μL of methanol containing the internal standards were supplemented. Supernatants were evaporated and residues were dissolved in 200<!--> <!-->μL of mobile phase. NPS identification in blood and tablets were performed using a qualitative liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) (Xevo TQ-XS, Waters).</div><div>Quantification was conducted on blood sample using a full scan analysis by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) (Q-Exactive®, Thermo Scientific) with standard solution of 2-MMC, bromazolam, 4-FMA, O-desmethyltramadol and quality controls.</div></div><div><h3>Results</h3><div>The post-mortem peripheral blood analysis revealed the following concentrations: bromazolam 308<!--> <!-->ng/mL, 2-MMC 12616<!--> <!-->ng/mL, O-desmethyltramadol 1410<!--> <!-->ng/mL, and 4-FMA 3176<!--> <!-->ng/mL. The identification of the tablets was consistent with the packaging label.</div></div><div><h3>Conclusion</h3><div>The death resulted from intoxication involving multiple NPS: 2-MMC, 4-FMA, O-desmethyltramadol, and bromazolam, with the latter being reported for the first time in France. The concentrations were higher than “lethal” concentrations reported in the scientific literature.</div><div>The accessibility of NPS leads to high-risk poly-consumption. Combining multiple substances from different chemical families, such as DBZD, is relatively common in the literature and can result in toxicological fatalities.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages S22-S23"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528826","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":"Quantitation using high-resolution mass spectrometry (HRMS)","authors":"Stephen Trobbiani","doi":"10.1016/j.toxac.2024.11.007","DOIUrl":"10.1016/j.toxac.2024.11.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To provide an overview of the technical differences between triple quadrupole (QQQ), quadrupole-time of flight (QTOF) and orbitrap mass spectrometers, then to provide a commentary on the quantitative performance of each instrument type, with examples from the author's own laboratory.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;QQQ instruments are primarily used in multiple reaction monitoring (MRM) mode in a targeted fashion, meaning compounds are only detected if pre-programmed in the acquisition method. QTOF and orbitrap instruments are commonly used in full scan mode and therefore capture a far larger amount of information, with all ionisable compounds capable of being detected, whether they are targeted or not.&lt;/div&gt;&lt;div&gt;QTOF spectra are typically composed of hundreds to thousands of individual ion packets, termed transients. The sensitivity of a QTOF method can be increased by summing a greater number of transients at the expense of scan speed. Orbitrap instruments are not affected by this but the resolution increases as a transient spends a longer time in the orbitrap, which reduces the scan speed.&lt;/div&gt;&lt;div&gt;In an orbitrap instrument, ions are first accumulated in the C-trap before being injected into the orbitrap analyser. To prevent overfilling of the orbitrap, the number of ions injected is controlled at this step. The resulting spectrum is then mathematically adjusted using automatic gain control (AGC) to maintain the quantitative accuracy of the data. AGC can improve the overall dynamic range across different spectra, but it may restrict the simultaneous measurement of very abundant and trace compounds within a single spectrum compared to QTOF instruments.&lt;/div&gt;&lt;div&gt;All three instrument designs commonly offer excellent precision, but modern QQQ instruments may provide superior sensitivity. The aspects of selectivity most relevant to quantitation are the amount of noise, and the frequency and abundance of interfering peaks from the matrix. It has been the experience of Forensic Science SA that extracted ion chromatograms from LC-QTOF data using appropriately narrow mass extraction windows usually show less noise and fewer interfering matrix peaks than MRM data from LC-QQQ methods.&lt;/div&gt;&lt;div&gt;Ease of use is subjective and can often be influenced by the experience of a person or the laboratory. Although HRMS instruments still have a reputation as being difficult to set up and use, at Forensic Science SA, most if not all scientists would consider it easier to set up a quantitative method using an LC-QTOF instrument, than determine and optimise MRMs on an LC-QQQ. Troubleshooting mass spectral issues that can affect quantitative results including co-eluting analyte suppression and formation of adducts, dimers and multiply charged ions is much simpler using full scan HRMS data.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;High-resolution mass spectrometers demonstrate excellent quantitative capabilities in addition to their ","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":"143528842","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":"Study of the involvement of amlodipine in the mechanism of death in a sample of patients at the University Hospital of Dijon","authors":"Alice Matheux ,&nbsp;Cassandra Amadieu ,&nbsp;Agathe Pasquet ,&nbsp;Irène Francois-Purssell ,&nbsp;Mélanie Loiseau ,&nbsp;Pascal Guerard","doi":"10.1016/j.toxac.2025.01.066","DOIUrl":"10.1016/j.toxac.2025.01.066","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Aim&lt;/h3&gt;&lt;div&gt;Amlodipine is a calcium channel blocker, used in cardiac pathologies. At toxic doses, amlodipine is responsible for death by cardiogenic shock and vasoplegia. Its pharmacokinetic properties suggest that post-mortem redistribution is possible, precluding interpretation based on living data (generally, between 6.5 and 20.9&lt;!--&gt; &lt;!--&gt;μg/L). Our objective was to determine the toxic concentrations of amlodipine post-mortem.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;Plasma samples were analyzed using a Q-Exactive Focus high-resolution mass spectrometer coupled to the Transcend LX2 UHPLC system (Thermo Scientific™). The various compounds in the liquid sample were extracted using in-line extraction due to two different TurboFlow™ columns, assembled in series. The first is a Cyclone™ and the second is a Phenyl™ (50&lt;!--&gt; &lt;!--&gt;mm&lt;!--&gt; &lt;!--&gt;×&lt;!--&gt; &lt;!--&gt;0.5&lt;!--&gt; &lt;!--&gt;mm) (Thermo Scientific™). After extraction, the compounds were separated by an analytical column, here, a phenylhyexyl™ column (100&lt;!--&gt; &lt;!--&gt;mm&lt;!--&gt; &lt;!--&gt;×&lt;!--&gt; &lt;!--&gt;2.1&lt;!--&gt; &lt;!--&gt;mm, 2.6&lt;!--&gt; &lt;!--&gt;μm) (Thermo Scientific™). The composition of mobile phase A was water with 0.1% formic acid and 2&lt;!--&gt; &lt;!--&gt;mM ammonium formate. For phase B, acetonitrile:methanol:water (49.5: 49.5: 1 v/v) with 0.1% formic acid and 2&lt;!--&gt; &lt;!--&gt;mM ammonium formate was used. Phase C was a mixture of acetone:acetonitrile:isopropanol (20: 40: 40 v/v). All solvents were of LCMS quality. The flow rate of the mixture of mobile phases A and B was set at 2&lt;!--&gt; &lt;!--&gt;mL/min for the TurboFlow™ columns and 0.5&lt;!--&gt; &lt;!--&gt;mL/min for the analytical column. The temperature of the analytical column was set at 40&lt;!--&gt; &lt;!--&gt;°C. Once the sample had been extracted and separated, it was transferred to the mass spectrometry system. The sample is ionized by an H-ESI probe, switching positive and negative. Amlodipine ionizes positively. The ions are analyzed by Full Scan MS and a ddMS&lt;sup&gt;2&lt;/sup&gt; analysis is applied to fragment the ions and obtain confirmation. The calibration curve ranged from 0.05 to 0.25&lt;!--&gt; &lt;!--&gt;μg/L. With the autopsy findings, we classified the data into three groups, independent of the toxicological findings: unrelated death (group 1), possibly related death (group 2), and Amlodipine-related death (group 3). All samples were post-mortem femoral whole blood.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Of the 31 cases, 1 case was classified in group 3 (Amlodipine concentration 275&lt;!--&gt; &lt;!--&gt;μg/L); 13 in group 2 (median concentration 83.0&lt;!--&gt; &lt;!--&gt;μg/L [42; 127.5]); and 17 cases in group 1 (median concentration 49&lt;!--&gt; &lt;!--&gt;μg/L [35.75; 85.25]).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our results show that in group 1 (death not related to Amlodipine), the median concentration of 49&lt;!--&gt; &lt;!--&gt;μg/L is 2.33 times higher than the therapeutic concentration observed in living patients.&lt;/div&gt;&lt;div&gt;According to our results, post-mortem concentrations below 85.25 (3rd quartile) μg/L, can be considered non-toxic. The use ","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S44"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529147","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":"Comparison of biological health among moderate-severe chemical veterans based on telomere length","authors":"Leila Nasiri ,&nbsp;Mohammad Reza Vaez-Mahdavi ,&nbsp;Tooba Ghazanfari ,&nbsp;Hossein Hassanpour ,&nbsp;Sussan Kaboudanian Ardestani","doi":"10.1016/j.toxac.2024.11.003","DOIUrl":"10.1016/j.toxac.2024.11.003","url":null,"abstract":"<div><h3>Background</h3><div>Sulfur mustard (SM) is a noxious gaseous substance that has been employed as a chemical warfare agent during armed conflicts. Individuals who have been exposed to SM continue to have adverse effects over an extended period of time. This study assessed the biological health of veterans with moderate-severe SM-chemical injuries categorized as having short or long telomere lengths (TL).</div></div><div><h3>Methods</h3><div>The calculation of the biological health score (BHS) involved the assessment of 18 biomarkers that are associated with the functioning of four physiological systems, namely the endocrine, inflammatory, cardiovascular, and metabolic systems, as well as two specific organs, namely the liver, and kidney. Forty-three people exposed to SM gas in 1987 at a moderate-severe level served as volunteers.</div></div><div><h3>Results</h3><div>The individuals with short TL subjected to moderate-to-severe SM had much-reduced testosterone levels and higher levels of LDL, cholesterol, and CRP compared to those with long TL. The results of principal component analysis revealed that testosterone had the highest degree of influence on intergroup variance among individuals who were subjected to moderate-severe levels of SM. Regarding moderate-severe SM-chemical veterans, our results demonstrated an inverse relationship between BHS and relative TL. Comparing the groups with short and long telomeres, the BHS was noticeably greater in the former.</div></div><div><h3>Conclusion</h3><div>The findings suggest that elevated BHS levels and reduced relative TL in veterans with moderate-severe SM exposure are indicative of diminished health quality. These indices may be valuable in assessing the health status of individuals exposed to SM, and using BHS and TL measurements might enhance the accuracy of such evaluations.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages 102-110"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527192","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":"Index des auteurs","authors":"","doi":"10.1016/S2352-0078(25)00131-3","DOIUrl":"10.1016/S2352-0078(25)00131-3","url":null,"abstract":"","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages S65-S67"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528638","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}