<div><h3>Aim</h3><div>To compare substances consumed by 2 populations of drivers – electro/trance festival (teknival) goers and drivers tested on random checks – by analyzing oral fluid samples collected on FLOQswabs™ devices.</div><div>To assess trends in new psychoactive substance (NPS) consumption during electro/trance music events such as teknival.</div></div><div><h3>Method</h3><div>Following driving checks during a teknival in the summer of 2024, our laboratory received 68 FLOQswabs™ samples for confirmatory analysis under French regulations. The first qualitative analysis, performed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), targeted amphetamine, methamphetamine, MDA, MDMA, MDEA, morphine, 6-monoacteylmorphine (6-MAM), cocaine, benzoylecgonine (BZE) and delta-9-tetrahydrocannabinol (THC). The previously reported protocol was implemented, according to the legal thresholds (Romeuf, Toxac, 2023, 35, 124–132). With the same injection, cannabidiol (CBD) and hexahydrocannabinol (HHC) were also targeted. In a second injection, unknown NPS screening was carried out by LC-MS/MS. The same methodology was applied to a representative population of 68 oral fluid samples collected on the same device during classic random checks for driving under influence of drugs.</div></div><div><h3>Results</h3><div>Sixty-six teknival samples were positive for at least one substance listed in the regulations, as were 64 from the random checks. Concerning cannabinoids, THC and CBD were more often detected in control samples (80.9% and 42.6%, respectively) than in teknival samples (61.8% and 26.5%). Morphine and 6-MAM were detected in only 1 control sample. Cocaine was systematically associated with its metabolite, BZE, with higher prevalence in teknival samples (44.1%) than in control samples (27.9%). Likewise, amphetamines, and particularly MDMA, were detected in 42.6% of teknival samples but in only 13.0% of control samples. On NPS analysis, ketamine was the most frequently detected substance in both populations, with higher prevalence in teknival samples (61.8%) than in controls (19.1%). In 98.0% of cases, ketamine was associated with at least one other substance. Few NPSs were found in the control population, with only diphenidine and HHC detected, in 1 case each; conversely, in the teknival population, dimethyltryptamine (DMT) and LSD were detected in 17.6% and 11.7% of cases, respectively. X-MMC and the benzofuran x-APB were identified in 2 cases each.</div></div><div><h3>Conclusion</h3><div>As expected, almost all swabs were positive for least at one substance, as confirmation is only required when the first oral fluid test by immunoassay is positive.</div><div>In both study populations, THC was the most frequently consumed substance. Cocaine and MDMA were consumed more frequently in the teknival context. Ketamine, which was detected in both populations, is one of the substances most commonly used in partying, particularly in combin
{"title":"Oral fluid analysis by LC-MS/MS: Comparison between drivers tested in random checks and after an electro/trance festival","authors":"Denis Dubois-Chabert , Amélie Poly , Ludovic Romeuf , Cécile Moreau , Camille Chatenay , Guillaume Hoizey , Charline Bottinelli","doi":"10.1016/j.toxac.2025.01.069","DOIUrl":"10.1016/j.toxac.2025.01.069","url":null,"abstract":"<div><h3>Aim</h3><div>To compare substances consumed by 2 populations of drivers – electro/trance festival (teknival) goers and drivers tested on random checks – by analyzing oral fluid samples collected on FLOQswabs™ devices.</div><div>To assess trends in new psychoactive substance (NPS) consumption during electro/trance music events such as teknival.</div></div><div><h3>Method</h3><div>Following driving checks during a teknival in the summer of 2024, our laboratory received 68 FLOQswabs™ samples for confirmatory analysis under French regulations. The first qualitative analysis, performed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), targeted amphetamine, methamphetamine, MDA, MDMA, MDEA, morphine, 6-monoacteylmorphine (6-MAM), cocaine, benzoylecgonine (BZE) and delta-9-tetrahydrocannabinol (THC). The previously reported protocol was implemented, according to the legal thresholds (Romeuf, Toxac, 2023, 35, 124–132). With the same injection, cannabidiol (CBD) and hexahydrocannabinol (HHC) were also targeted. In a second injection, unknown NPS screening was carried out by LC-MS/MS. The same methodology was applied to a representative population of 68 oral fluid samples collected on the same device during classic random checks for driving under influence of drugs.</div></div><div><h3>Results</h3><div>Sixty-six teknival samples were positive for at least one substance listed in the regulations, as were 64 from the random checks. Concerning cannabinoids, THC and CBD were more often detected in control samples (80.9% and 42.6%, respectively) than in teknival samples (61.8% and 26.5%). Morphine and 6-MAM were detected in only 1 control sample. Cocaine was systematically associated with its metabolite, BZE, with higher prevalence in teknival samples (44.1%) than in control samples (27.9%). Likewise, amphetamines, and particularly MDMA, were detected in 42.6% of teknival samples but in only 13.0% of control samples. On NPS analysis, ketamine was the most frequently detected substance in both populations, with higher prevalence in teknival samples (61.8%) than in controls (19.1%). In 98.0% of cases, ketamine was associated with at least one other substance. Few NPSs were found in the control population, with only diphenidine and HHC detected, in 1 case each; conversely, in the teknival population, dimethyltryptamine (DMT) and LSD were detected in 17.6% and 11.7% of cases, respectively. X-MMC and the benzofuran x-APB were identified in 2 cases each.</div></div><div><h3>Conclusion</h3><div>As expected, almost all swabs were positive for least at one substance, as confirmation is only required when the first oral fluid test by immunoassay is positive.</div><div>In both study populations, THC was the most frequently consumed substance. Cocaine and MDMA were consumed more frequently in the teknival context. Ketamine, which was detected in both populations, is one of the substances most commonly used in partying, particularly in combin","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages S45-S46"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529297","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}
<div><h3>Aim</h3><div>In post-mortem toxicology, analysis of different biological matrices is crucial to confirm what has been identified in blood. Nevertheless, conventional matrices can be difficult to analyze with standard extraction protocol or missing. The concept of bladder washing has been introduced in 2022 at the TIAFT annual meeting <span><span>[1]</span></span>. The evaluation was carried out after emptying bladder and then rewashing it. But real-life conditions can be difficult with putrefied, polytraumatized or carbonized corpses. The first bladder wash was performed in Grenoble in November 2022 by forensic pathologist team and is now performed routinely. The authors aim to describe bladder wash sampling technique and present a critical evaluation in current post-mortem toxicology practice.</div></div><div><h3>Method</h3><div>Bladder wash was achieved when bladder was empty, with a 5<!--> <!-->mL wash of 0.9% NaCl solution during the forensic autopsy.</div><div>This study included authentic bladder washes from November 2022 to November 2024. Toxicological analysis were performed on request of police officers or prosecutors. The analysis was carried out in LC-MS/MS, LC-HRMS for screenings of drugs of abuses and medications and GC-FID for volatiles.</div><div>Sample preparation for screening consisted in a phospholipid removal using Ostro® plates. Targeted LC-MS/MS screenings were carried out on an Acquity UPLC HSS C18 column (2.1<!--> <!-->×<!--> <!-->100<!--> <!-->mm) and a Xevo TQ-XS mass spectrometer (Waters). Targeted LC-HRMS screenings were carried out on an Accucore Phenyl-Hexyl column (2.1<!--> <!-->×<!--> <!-->100<!--> <!-->mm) and an Exploris 120 (Thermo Scientific) mass spectrometer.</div><div>To evaluate the efficiency of the wash, creatininuria and proteinuria assays were carried out on an Atellica system (Siemens Healthineers®) using automated enzymatic and colorimetric techniques.</div></div><div><h3>Results</h3><div>This study included 63 authentic bladder washes. Mean bladder wash volume was 2,3<!--> <!-->mL. Subjects were aged from 1 month to 92 years with mean body mass index of 26.6. Mean post-mortem interval was 2.5 days.</div><div>No substance was identified in 8 washes. Among the substances identified, psychotropic drugs (lithium, cyamemaine, venlafaxine, diazepam, vortioxetine, valproic acid, pregabaline…), drugs of abuse (cocaine, MDMA, THC-COOH, oxycodone, methadone, morphine…), cardiotropic and antidiabetic medications (amlodipine, sotalol, irbesartan, amiodarone, ramiprilat, metformine, sitagliptine, gliclazide…), anesthesic drugs (sufentanil, midazolam, laudanosine, etomidate, propofol, ketamine) or metabolites (ethylglucuronide, cotinine, acetone) were correctly detected in bladder wash.</div><div>Between blood and bladder wash results, a concordance of 76.2% was observed in this study, including ethanol. In 15.9% cases, bladder wash was negative and only ethanol was identified in blood. Therefore, ethanol
{"title":"Bladder wash as an alternative specimen for post-mortem toxicology: Feedback from 63 authentic samples","authors":"Théo Willeman , Bérénice Royez , Jeremy Borges , Coralie Boudin , François Paysant , Françoise Stanke-Labesque , Hélène Eysseric-Guerin , Virginie Scolan","doi":"10.1016/j.toxac.2025.01.060","DOIUrl":"10.1016/j.toxac.2025.01.060","url":null,"abstract":"<div><h3>Aim</h3><div>In post-mortem toxicology, analysis of different biological matrices is crucial to confirm what has been identified in blood. Nevertheless, conventional matrices can be difficult to analyze with standard extraction protocol or missing. The concept of bladder washing has been introduced in 2022 at the TIAFT annual meeting <span><span>[1]</span></span>. The evaluation was carried out after emptying bladder and then rewashing it. But real-life conditions can be difficult with putrefied, polytraumatized or carbonized corpses. The first bladder wash was performed in Grenoble in November 2022 by forensic pathologist team and is now performed routinely. The authors aim to describe bladder wash sampling technique and present a critical evaluation in current post-mortem toxicology practice.</div></div><div><h3>Method</h3><div>Bladder wash was achieved when bladder was empty, with a 5<!--> <!-->mL wash of 0.9% NaCl solution during the forensic autopsy.</div><div>This study included authentic bladder washes from November 2022 to November 2024. Toxicological analysis were performed on request of police officers or prosecutors. The analysis was carried out in LC-MS/MS, LC-HRMS for screenings of drugs of abuses and medications and GC-FID for volatiles.</div><div>Sample preparation for screening consisted in a phospholipid removal using Ostro® plates. Targeted LC-MS/MS screenings were carried out on an Acquity UPLC HSS C18 column (2.1<!--> <!-->×<!--> <!-->100<!--> <!-->mm) and a Xevo TQ-XS mass spectrometer (Waters). Targeted LC-HRMS screenings were carried out on an Accucore Phenyl-Hexyl column (2.1<!--> <!-->×<!--> <!-->100<!--> <!-->mm) and an Exploris 120 (Thermo Scientific) mass spectrometer.</div><div>To evaluate the efficiency of the wash, creatininuria and proteinuria assays were carried out on an Atellica system (Siemens Healthineers®) using automated enzymatic and colorimetric techniques.</div></div><div><h3>Results</h3><div>This study included 63 authentic bladder washes. Mean bladder wash volume was 2,3<!--> <!-->mL. Subjects were aged from 1 month to 92 years with mean body mass index of 26.6. Mean post-mortem interval was 2.5 days.</div><div>No substance was identified in 8 washes. Among the substances identified, psychotropic drugs (lithium, cyamemaine, venlafaxine, diazepam, vortioxetine, valproic acid, pregabaline…), drugs of abuse (cocaine, MDMA, THC-COOH, oxycodone, methadone, morphine…), cardiotropic and antidiabetic medications (amlodipine, sotalol, irbesartan, amiodarone, ramiprilat, metformine, sitagliptine, gliclazide…), anesthesic drugs (sufentanil, midazolam, laudanosine, etomidate, propofol, ketamine) or metabolites (ethylglucuronide, cotinine, acetone) were correctly detected in bladder wash.</div><div>Between blood and bladder wash results, a concordance of 76.2% was observed in this study, including ethanol. In 15.9% cases, bladder wash was negative and only ethanol was identified in blood. Therefore, ethanol","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S40"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529142","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}
Pub Date : 2025-03-01DOI: 10.1016/j.toxac.2025.01.010
Nik De Brabanter, Pauline Herroelen, Eva Dewandelaere, Saartje Gijbels, Cindy Maeren, Lisa Van Langendonck, Hilde Vanpoucke, Inge De Cuyper, Dieter De Smet, Ansofie Decavele
In November 2022 an intoxicated patient was admitted to the AZ Delta General Hospital emergency department declaring he smoked Flakka. Initially appearing as an isolated case, it quickly became clear that this was the beginning of a regional emergence. In the following weeks, several patients presented with symptoms ranging from excited delirium syndrome and psychosis to coma, all linked to the use of Flakka. This surge necessitated a coordinated response at multiple levels: hospital, regional, and national.
To address this, our toxicology lab rapidly developed an LC-MS/MS method to selectively detect the cathinones alpha-PVP, alpha-PHP and alpha-PHiP in urine and implemented in the routine tox screening. To date, this method has been used to identify over 100 alpha-PHiP positive patients and enabled correct monitoring of the situation.
In parallel, actions were initiated along multiple axes. In the hospital, close cooperation with e.g. the emergency department led to effective follow-up and the initiation of patient management plans.
On a regional level, regular consultations were established with local stakeholders: the city council, law enforcement and healthcare providers. The focus here was on ensuring the exchange of accurate and up-to-date information on the issue, as well as streamlining external communication.
The toxicology lab's findings were continuously reported to Belgian Early Warning System (BEWSD). This ensured that the data collected at the regional level induced national responses.
One and a half years after the first case, our laboratory results indicate that alpha-PHiP has disappeared from the regional drug market. Interdisciplinary collaboration and rapid, open communication have proven to be crucial in tackling and containing this surge. However, continued monitoring of the (regional) drug market for potential successors to alpha-PHiP remains essential. While the toxicology lab plays a key role in this effort, progress depends on the activation of a multidisciplinary network.
{"title":"From Lab to action: The role of a General Hospital Toxicology Lab in multidisciplinary responses to Flakka's regional emergence","authors":"Nik De Brabanter, Pauline Herroelen, Eva Dewandelaere, Saartje Gijbels, Cindy Maeren, Lisa Van Langendonck, Hilde Vanpoucke, Inge De Cuyper, Dieter De Smet, Ansofie Decavele","doi":"10.1016/j.toxac.2025.01.010","DOIUrl":"10.1016/j.toxac.2025.01.010","url":null,"abstract":"<div><div>In November 2022 an intoxicated patient was admitted to the AZ Delta General Hospital emergency department declaring he smoked Flakka. Initially appearing as an isolated case, it quickly became clear that this was the beginning of a regional emergence. In the following weeks, several patients presented with symptoms ranging from excited delirium syndrome and psychosis to coma, all linked to the use of Flakka. This surge necessitated a coordinated response at multiple levels: hospital, regional, and national.</div><div>To address this, our toxicology lab rapidly developed an LC-MS/MS method to selectively detect the cathinones alpha-PVP, alpha-PHP and alpha-PHiP in urine and implemented in the routine tox screening. To date, this method has been used to identify over 100 alpha-PHiP positive patients and enabled correct monitoring of the situation.</div><div>In parallel, actions were initiated along multiple axes. In the hospital, close cooperation with e.g. the emergency department led to effective follow-up and the initiation of patient management plans.</div><div>On a regional level, regular consultations were established with local stakeholders: the city council, law enforcement and healthcare providers. The focus here was on ensuring the exchange of accurate and up-to-date information on the issue, as well as streamlining external communication.</div><div>The toxicology lab's findings were continuously reported to Belgian Early Warning System (BEWSD). This ensured that the data collected at the regional level induced national responses.</div><div>One and a half years after the first case, our laboratory results indicate that alpha-PHiP has disappeared from the regional drug market. Interdisciplinary collaboration and rapid, open communication have proven to be crucial in tackling and containing this surge. However, continued monitoring of the (regional) drug market for potential successors to alpha-PHiP remains essential. While the toxicology lab plays a key role in this effort, progress depends on the activation of a multidisciplinary network.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages S12-S13"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529153","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}
Pub Date : 2025-03-01DOI: 10.1016/j.toxac.2024.12.004
Pascal Kintz , Nadia Arbouche
{"title":"Pikachu : la nouvelle drogue du violeur ?","authors":"Pascal Kintz , Nadia Arbouche","doi":"10.1016/j.toxac.2024.12.004","DOIUrl":"10.1016/j.toxac.2024.12.004","url":null,"abstract":"","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Pages 1-3"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527299","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}
Pub Date : 2025-03-01DOI: 10.1016/j.toxac.2025.01.029
Maxime Alexandre , Romain Pelletier , Brendan Le Dare , Isabelle Morel , Renaud Bouvet , Thomas Gicquel
Aim
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.
Method
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).
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.
Results
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.
Conclusion
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.
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.
{"title":"Death by intoxication involving various new psychoactive substances including bromazolam","authors":"Maxime Alexandre , Romain Pelletier , Brendan Le Dare , Isabelle Morel , Renaud Bouvet , 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}
Pub Date : 2025-03-01DOI: 10.1016/j.toxac.2025.01.056
Francesco Paolo Busardò
Objective
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.
Introduction
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.
Methods
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.
Results
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.
The presence of one or more specific biomarkers reinforces traditional analysis (segmental hair analysis of GHB and determination of a ratio).
These results underline the importance of new potential biomarkers of consumption in improving the reliability and specificity of GHB analysis in hair.
Discussion
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.
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.
Conclusion
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.
{"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}
Le dosage capillaire du plomb est souvent jugé peu pertinent sur le plan clinique en raison de la contamination externe importante, qui peut influencer les résultats. Toutefois, cet article présente un cas d’intoxication familiale sévère où l’analyse capillaire du plomb a permis de révéler une source de contamination méconnue, apportant ainsi des informations décisives.
Méthodes
Description de l’histoire clinique et des investigations analytiques cliniques et environnementales. Le plomb (Pb) a été mesuré par spectrométrie de masse à plasma à couplage inductif (ICP-MS), sur un ICAP-TQ de Thermo Scientific® (Plateforme AEM2, Université de Rennes 1/Laboratoire de Biochimie, CHU de Rennes).
Résultats
Une femme a été prise en charge pour une intoxication au plomb sévère. Les explorations ont montré que certains membres de la famille présentaient également des niveaux de contamination élevés. Aucun facteur professionnel, domestique ou environnemental évocateur n’a pu être identifié initialement. Des investigations environnementales approfondies, incluant des analyses de ratios isotopiques, n’ont pas permis de déterminer la source de la contamination. Cependant, une analyse capillaire a montré une augmentation soudaine des niveaux de plomb dans les cheveux, remontant à la fin de l’été précédent l’intoxication, avec une concentration capillaire maximale de 10,07 μg/g de cheveu. Un interrogatoire détaillé a alors révélé une source de contamination jusque-là ignorée : le meulage et la pose de carrelages traditionnels de type « zellige » à cette même période. L’analyse des zelliges a montré de fortes concentrations de plomb dans leur partie émaillée. La contamination avait été majorée chez certains membres de la famille par une onychophagie importante. L’évolution des niveaux de plomb était cohérente avec cette exposition et a permis de déclencher une alerte sanitaire concernant le risque associé à ces carrelages à la mode, qui représentent une source potentiellement conséquente de contamination à l’échelon national.
Conclusion
Le dosage du plomb capillaire est mal corrélé avec la plombémie, en particulier lorsque celle-ci est modérément élevée (< 120 μg/L) [ATSDR, Toxicological Profile for Lead, août 2020]. La contamination externe importante rend cette technique le plus souvent inutilisable pour l’interprétation clinique. Toutefois, dans cette situation particulière, l’analyse capillaire a été déterminante pour identifier la source de la contamination, que les tests isotopiques seuls n’avaient pas permis de faire. Bien que le dosage du plomb capillaire soit le plus souvent peu utilisable en clinique en raison des risques de contamination externe, il peut apporter des informations chronologiques décisives dans certaines situations spécifiques pour identifier la source de la contamination.
{"title":"Place du dosage capillaire du plomb dans l’identification d’une source d’exposition lors d’un cas d’intoxication","authors":"Jérôme Langrand , Chloé Bruneau , Hervé Laborde-Casterot , Marie-Laure Island , Martine Ropert-Bouchet","doi":"10.1016/j.toxac.2025.01.085","DOIUrl":"10.1016/j.toxac.2025.01.085","url":null,"abstract":"<div><h3>Objectifs</h3><div>Le dosage capillaire du plomb est souvent jugé peu pertinent sur le plan clinique en raison de la contamination externe importante, qui peut influencer les résultats. Toutefois, cet article présente un cas d’intoxication familiale sévère où l’analyse capillaire du plomb a permis de révéler une source de contamination méconnue, apportant ainsi des informations décisives.</div></div><div><h3>Méthodes</h3><div>Description de l’histoire clinique et des investigations analytiques cliniques et environnementales. Le plomb (Pb) a été mesuré par spectrométrie de masse à plasma à couplage inductif (ICP-MS), sur un ICAP-TQ de Thermo Scientific® (Plateforme AEM2, Université de Rennes 1/Laboratoire de Biochimie, CHU de Rennes).</div></div><div><h3>Résultats</h3><div>Une femme a été prise en charge pour une intoxication au plomb sévère. Les explorations ont montré que certains membres de la famille présentaient également des niveaux de contamination élevés. Aucun facteur professionnel, domestique ou environnemental évocateur n’a pu être identifié initialement. Des investigations environnementales approfondies, incluant des analyses de ratios isotopiques, n’ont pas permis de déterminer la source de la contamination. Cependant, une analyse capillaire a montré une augmentation soudaine des niveaux de plomb dans les cheveux, remontant à la fin de l’été précédent l’intoxication, avec une concentration capillaire maximale de 10,07<!--> <!-->μg/g de cheveu. Un interrogatoire détaillé a alors révélé une source de contamination jusque-là ignorée : le meulage et la pose de carrelages traditionnels de type « zellige » à cette même période. L’analyse des zelliges a montré de fortes concentrations de plomb dans leur partie émaillée. La contamination avait été majorée chez certains membres de la famille par une onychophagie importante. L’évolution des niveaux de plomb était cohérente avec cette exposition et a permis de déclencher une alerte sanitaire concernant le risque associé à ces carrelages à la mode, qui représentent une source potentiellement conséquente de contamination à l’échelon national.</div></div><div><h3>Conclusion</h3><div>Le dosage du plomb capillaire est mal corrélé avec la plombémie, en particulier lorsque celle-ci est modérément élevée (< 120<!--> <!-->μg/L) [ATSDR, <em>Toxicological Profile for Lead</em>, août 2020]. La contamination externe importante rend cette technique le plus souvent inutilisable pour l’interprétation clinique. Toutefois, dans cette situation particulière, l’analyse capillaire a été déterminante pour identifier la source de la contamination, que les tests isotopiques seuls n’avaient pas permis de faire. Bien que le dosage du plomb capillaire soit le plus souvent peu utilisable en clinique en raison des risques de contamination externe, il peut apporter des informations chronologiques décisives dans certaines situations spécifiques pour identifier la source de la contamination.</div></div>","PeriodicalId":23170,"journal":{"name":"Toxicologie Analytique et Clinique","volume":"37 1","pages":"Page S55"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528831","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}
<div><h3>Aim</h3><div>To formally identify the isomers of chloromethcathinone (x-CMC).</div></div><div><h3>Method</h3><div>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).</div></div><div><h3>Results</h3><div>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<!--> <!-->><!--> <!-->110.9, 138.9<!--> <!-->><!--> <!-->75.0 and 112.9<!--> <!-->><!--> <!-->75.0, and for LC-MS/MS 197.9<!--> <!-->><!--> <!-->145.0 and 197.9<!--> <!-->><!--> <!-->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<!--> <!-->min and 3.52<!--> <!-->min for 3-CMC and 4-CMC, respectively, on LC-MS/MS. As well as being discriminated by RT, 3-CMC (6.32<!--> <!-->min) and 4-CMC (6.54<!--> <!-->min) were clearly distinguishable on LC-DAD/MS by their absorption spectra. Absorbance maxima were observed at wavelengths of 210 and 250<!--> <!-->nm for 3-CMC and 197 and 262<!--> <!-->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.</div></div><div><h3>Conclusion</h3><div>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
{"title":"LC-DAD: A tool from the past to identify isomers of new psychoactives substances. Application to chloromethcathinones","authors":"Pauline Baradian , Camille Chatenay , Guillaume Hoizey , Laurent Fanton , Charline Bottinelli","doi":"10.1016/j.toxac.2025.01.068","DOIUrl":"10.1016/j.toxac.2025.01.068","url":null,"abstract":"<div><h3>Aim</h3><div>To formally identify the isomers of chloromethcathinone (x-CMC).</div></div><div><h3>Method</h3><div>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).</div></div><div><h3>Results</h3><div>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<!--> <!-->><!--> <!-->110.9, 138.9<!--> <!-->><!--> <!-->75.0 and 112.9<!--> <!-->><!--> <!-->75.0, and for LC-MS/MS 197.9<!--> <!-->><!--> <!-->145.0 and 197.9<!--> <!-->><!--> <!-->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<!--> <!-->min and 3.52<!--> <!-->min for 3-CMC and 4-CMC, respectively, on LC-MS/MS. As well as being discriminated by RT, 3-CMC (6.32<!--> <!-->min) and 4-CMC (6.54<!--> <!-->min) were clearly distinguishable on LC-DAD/MS by their absorption spectra. Absorbance maxima were observed at wavelengths of 210 and 250<!--> <!-->nm for 3-CMC and 197 and 262<!--> <!-->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.</div></div><div><h3>Conclusion</h3><div>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}
Pub Date : 2025-03-01DOI: 10.1016/j.toxac.2024.11.007
Stephen Trobbiani
<div><h3>Objective</h3><div>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.</div></div><div><h3>Discussion</h3><div>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.</div><div>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.</div><div>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.</div><div>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.</div><div>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.</div></div><div><h3>Conclusion</h3><div>High-resolution mass spectrometers demonstrate excellent quantitative capabilities in addition to their
{"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":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Discussion</h3><div>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.</div><div>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.</div><div>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.</div><div>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.</div><div>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.</div></div><div><h3>Conclusion</h3><div>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}
Pub Date : 2025-03-01DOI: 10.1016/j.toxac.2025.01.014
Michael Scholz
<div><div>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.</div><div>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.</div><div>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.</div><div>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
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