Forensic Toxicology最新文献

{"title":"Comparative GC-MS and LC-MS/MS characterization of four 8-hydroxyhexahydrocannabinol stereoisomers and their TMS derivatives.","authors":"Kei Ieuji, Masaru Kondo, Kayo Nakamura, Hideyo Takahashi","doi":"10.1007/s11419-026-00785-0","DOIUrl":"https://doi.org/10.1007/s11419-026-00785-0","url":null,"abstract":"<p><strong>Purpose: </strong>Hexahydrocannabinol (HHC) is an emerging semi-synthetic cannabinoid, but analytical data for all structurally confirmed stereoisomers of its hydroxylated metabolites remain limited. In this study, we synthesized all four stereoisomers of 8-hydroxyhexahydrocannabinol (8-OH-HHC) and comparatively characterized them, together with their trimethylsilyl (TMS) derivatives, by gas chromatography mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A particular analytical advantage of the present work is that it includes LC-MS/MS data for (8S,9R)-8-OH-HHC, for which no standard-based analytical data was previously available.</p><p><strong>Methods: </strong>Four synthetic 8-OH-HHC stereoisomers were analyzed by GC-MS and LC-MS/MS. For GC-MS, both underivatized compounds and their TMS derivatives were examined. Retention behavior, electron ionization mass spectra, and LC-MS/MS transitions were compared among the stereoisomers.</p><p><strong>Results: </strong>Under the tested GC conditions, the four stereoisomers and their TMS derivatives showed different retention times, although some differences were small and should be interpreted cautiously. Two pairs of stereoisomers exhibited similar electron ionization fragmentation patterns, whereas one pair showed differences in the relative abundances of selected ions. In addition to providing GC-MS data for all four underivatized stereoisomers, this study also provides GC retention and EI mass spectral data for all four TMS derivatives and a comparative evaluation of relative ion abundances among these closely related isomers. In LC-MS/MS, the stereoisomers showed partially overlapping transition patterns and closely eluting peaks under the tested conditions.</p><p><strong>Conclusions: </strong>These data provide a comparative analytical reference dataset for four structurally confirmed 8-OH-HHC stereoisomers and their TMS derivatives and may support future forensic studies of HHC-related compounds.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of xylazine, xylazine-4-hydroxy, and 2,6-dimethylaniline in canine urine: veterinary and forensic applications in two suspected poisoning cases.","authors":"Zeynep Arslan, Cenk Bulut, Bengü Bilgiç, Yeter Erol Öztürk, Mehmet Erman Or, Zeynep Türkmen","doi":"10.1007/s11419-026-00784-1","DOIUrl":"https://doi.org/10.1007/s11419-026-00784-1","url":null,"abstract":"<p><strong>Purpose: </strong>Xylazine, an α²-adrenergic agonist, is widely used in veterinary medicine for anesthesia, sedation, and analgesia. However, non-therapeutic use, overdose, and deliberate administration may pose serious health risks to animals, necessitating reliable detection methods for both clinical and forensic purposes.</p><p><strong>Methods: </strong>In this study, a liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method was developed and fully validated for the determination of xylazine and its metabolites in canine urine.</p><p><strong>Results: </strong>The method exhibited excellent selectivity and linearity over the range of 0.05-100 ng/mL, with coefficients of determination (R²) ≥ 0.9989. Recovery values ranged from 70.3% to 93.4%, with matrix effect values between 78.6% and 95.6%, and process efficiency values ranging from 74.9% to 94.3%. Precision and accuracy values were within ± 15% at all quality control levels, and the analytes were stable under all tested conditions (+ 8 °C for 3 days, + 4 °C and - 20 °C for 5 days). In two forensic cases, urine samples collected from canines presenting with unconsciousness contained xylazine and its metabolites, while no other sedative or toxic agents were detected.</p><p><strong>Conclusion: </strong>The presence of both 2,6-dimethylaniline (DMA) and 4-hydroxyxylazine supports the necessity for including metabolite analysis in exposure assessment. This study highlights the applicability of LC-HRMS for the detection of xylazine-related compounds in canine urine and its potential use in veterinary and forensic toxicology contexts.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broad-spectrum LC-MS/MS hair analysis for monitoring recreational drug use in electronic dance music festival attendees.","authors":"Bruno Pereira Dos Santos, Patrícia de Souza Schwarz, Letícia Birk, Ana Miguel Fonseca Pego, Sarah Eller, Tiago Franco de Oliveira","doi":"10.1007/s11419-026-00787-y","DOIUrl":"https://doi.org/10.1007/s11419-026-00787-y","url":null,"abstract":"<p><strong>Purpose: </strong>Hair toxicological analysis enables the verification of long-term drug use monitoring and supports epidemiological studies. In recreational contexts, multi-analyte methods are crucial for accurately characterizing consumption patterns. The present work aimed to develop and validate an LC-MS/MS method for the analysis of 47 drugs of abuse and related compounds in hair samples.</p><p><strong>Methods: </strong>A 20 mg hair aliquot was incubated with methanol at 40 °C for 16 h. The supernatant was dried and injected into the LC-MS/MS system. The monitored substances were amphetamines, cocaine and related compounds, cannabinoids, opioids, hallucinogens, synthetic cathinones, synthetic phenethylamines, and synthetic cannabinoids. The method was validated in accordance with international recommendations and subsequently applied to 81 hair samples collected at Brazilian electronic dance music festivals.</p><p><strong>Results: </strong>The method had limits of detection of 0.5-5 pg/mg and limits of quantification of 5-50 pg/mg. All compounds showed suitable linearity (R² > 0.9903). The precision assays showed CV% from 1.3% to 19.0%, while accuracy varied from 80.1% to 119.8%. All analyzed samples presented at least one of the target compounds. The most prevalent substances were MDA (85.2%), benzoylecgonine (84.0%), cocaine (84.0%), MDMA (72.8%), and Δ⁹-tetrahydrocannabinol (56.8%).</p><p><strong>Conclusions: </strong>This study presented a validated multi-analyte method for the analysis of drugs of abuse and related compounds in hair. Application of the method to a cohort of electronic dance music festival attendees revealed widespread polysubstance exposure, with a notable predominance of MDA. The findings support the role of toxicological analysis as a valuable tool for toxicosurveillance.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic evaluation of derivatization strategies and GC column polarity for reliable GC-MS separation of amphetamine and phenethylamine in putrefied postmortem samples.","authors":"Akira Namera, Kana Murata, Takeshi Saito, Maho Kawamura, Akihiro Nakamoto, Takahiro Harada, Masataka Nagao","doi":"10.1007/s11419-026-00779-y","DOIUrl":"https://doi.org/10.1007/s11419-026-00779-y","url":null,"abstract":"<p><strong>Purpose: </strong>The reliable identification of amphetamine in degraded biological samples is often complicated by the presence of putrefactive amines, such as phenethylamine, which exhibit similar physicochemical properties and can interfere with chromatographic separation. This study aimed to systematically evaluate the conditions of gas chromatography-mass spectrometry (GC-MS), including derivatization methods and analytical column selection, to achieve effective separation and identification of amphetamine in the presence of phenethylamine.</p><p><strong>Methods: </strong>Various derivatization approaches, including acylation, alkoxycarbonylation, silylation, and pentafluorobenzylation, were examined in combination with non-polar, slightly polar, and semi-polar GC columns. The chromatographic behavior of amphetamine and phenethylamine, including the retention time, peak shape, and formation of mono- or di-substituted derivatives, was systematically assessed to optimize separation and mass spectral identification.</p><p><strong>Results: </strong>Alkoxycarbonylation, silylation, and alkylation produced overlapping peaks, mixed derivatives, or unreacted compounds, thereby limiting their reliable identification. Acyl derivatization allowed for effective separation using non-polar and semi-polar columns, with the non-polar column minimizing peak tailing that is commonly caused by high phenethylamine concentrations. Differences in the elution order were observed between column types, and semi-polar columns provided satisfactory chromatographic resolution and high-quality mass spectra, consistent with spectral databases.</p><p><strong>Conclusions: </strong>Successful GC-MS identification of amphetamine in putrefied samples requires careful selection of the derivatization chemistry and GC column polarity. Acyl derivatization combined with an appropriate column choice enables reliable separation from phenethylamine, improves spectral quality, and enhances the evidential value of forensic analysis.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of 3-chlorophenmetrazine (3-CPM) from new psychoactive substances products and analytical differentiation from the ortho- and para-substituted isomers.","authors":"Kazue Tanaka, Miho Sakamoto, Yoko Ichikawa-Kaji, Yuki Saeki, Takako Yamazaki, Tomoko Urade, Machiko Nagashima, Toshinari Suzuki, Ruri Kikura-Hanajiri, Kayo Nakamura, Haruhiko Fukaya, Jun'ichi Nakajima, Akiko Inomata, Hideyo Takahashi","doi":"10.1007/s11419-026-00780-5","DOIUrl":"https://doi.org/10.1007/s11419-026-00780-5","url":null,"abstract":"<p><strong>Purpose: </strong>3-Chlorophenmetrazine (3-CPM) is a phenmetrazine analog that has been detected in new psychoactive substance (NPS) products sold on the market. The objective of this study was to perform an analytical characterization of 3-CPM identified in NPS products. In addition, 2-chlorophenmetrazine (2-CPM) and 4-chlorophenmetrazine (4-CPM), which are positional isomers of 3-CPM, were synthesized, and analytical methods for their differentiation were validated to prevent misidentification of the three CPM isomers.</p><p><strong>Methods: </strong>Samples were analyzed using liquid chromatography with photodiode array detection (LC/PDA), liquid chromatography-high resolution mass spectrometry (LC/HRMS), gas chromatography-mass spectrometry (GC/MS), gas chromatography-high resolution mass spectrometry (GC/HRMS), nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography.</p><p><strong>Results: </strong>Four NPS products sold between October 2022 and February 2023 were found to mainly contain trans-3-CPM, as determined by NMR analysis. Quantitative analysis showed that the powder and crystal products contained approximately 0.86-1.98 g of 3-CPM per package, whereas the tablet product contained approximately 0.10 g of 3-CPM per tablet. In chromatographic analyses, 2-CPM, 3-CPM, and 4-CPM were distinguishable based on retention times using octadecylsilyl silica gel (ODS) and phenyl columns for LC/PDA, and HP-5ms and CycloSil-B columns for GC/MS. Small differences were observed between UV spectra of 2-CPM/3-CPM and that of 4-CPM. Furthermore, 2-CPM produced a characteristic product ion in the LC/HRMS spectrum.</p><p><strong>Conclusions: </strong>The three positional isomers (2-, 3-, and 4-CPM) can be differentiated using LC and GC-based analytical methods. The analytical data presented in this study will facilitate the structural elucidation and accurate identification of novel phenmetrazine analogs in future investigations.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Misoprostol exposure disrupts neural tube development in a chick embryo model: experimental implications for forensic toxicology.","authors":"Ugur Kayhan, Abdülkadir Bilir, Tolga Ertekin, Emre Atay, Zafer Söylemez, Fatma Firat, Zafer Liman","doi":"10.1007/s11419-026-00778-z","DOIUrl":"https://doi.org/10.1007/s11419-026-00778-z","url":null,"abstract":"<p><strong>Purpose: </strong>Misoprostol is a uterotonic agent widely used in obstetric and gynecological practice and is of forensic importance due to its involvement in pregnancy termination cases and related medico-legal evaluations. This study aimed to investigate the effects of misoprostol exposure on neural tube development during early embryogenesis using a chick embryo model.</p><p><strong>Methods: </strong>Early-stage chick embryos were exposed to different doses of misoprostol. Neural tube development was evaluated through morphometric, immunohistochemical, and molecular analyses. Morphological changes were assessed, while the expression of proliferating cell nuclear antigen (PCNA) and caspase-3 was examined immunohistochemically. In addition, the expression levels of selected neurodevelopment-related genes were analyzed.</p><p><strong>Results: </strong>Morphometric assessments revealed neural tube closure defects and developmental delay in the misoprostol-exposed groups. Immunohistochemical analyses demonstrated decreased PCNA expression and increased caspase-3 expression compared with controls. Molecular analyses showed significant alterations in the expression of genes associated with neurodevelopment.</p><p><strong>Conclusion: </strong>Misoprostol exposure adversely affected neural tube development by disrupting cellular proliferation, apoptosis, and neurodevelopment-related gene expression during early embryogenesis. These findings suggest potential developmental risks associated with early embryonic exposure to misoprostol and may contribute to forensic and medico-legal evaluations of prenatal exposure cases.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postmortem distribution of thiamethoxam in biological fluids and solid tissues measured through liquid chromatography-tandem mass spectrometry using the standard addition method.","authors":"Kazumichi Kakazu, Kenji Ninomiya, Chiaki Fuke, Natsuki Ikematsu, Maki Fukasawa, Mio Takayama","doi":"10.1007/s11419-026-00765-4","DOIUrl":"10.1007/s11419-026-00765-4","url":null,"abstract":"<p><p>PURPOSE: To our knowledge, no previous reports have described the postmortem distribution of thiamethoxam in fatal cases. This study aimed to quantify thiamethoxam in biological fluids and solid tissues from a suicide involving ingestion of Actara® insecticide (10% thiamethoxam) using liquid chromatography–tandem mass spectrometry (LC–MS/MS). METHODS: Biological fluids and solid tissue homogenates were deproteinized with methanol. Thiamethoxam-d4 served as the internal standard. The standard addition method was used for quantification. RESULTS: Thiamethoxam was detected in all analyzed specimens, including 4 biological fluids, 11 solid tissues, and stomach contents. Thiamethoxam concentrations in each specimen, excluding the stomach contents, ranged from 2.5 to 53.6 µg/mL(g). The correlation coefficients (r2) for the calibration curves ranged from 0.9934 to 0.9996. Intraday and interday variability were < 8.9% and < 11.1%, respectively. CONCLUSIONS: Thiamethoxam was quantified in biological fluids and solid tissues obtained at autopsy using LC–MS/MS with standard addition. To our knowledge, this is the first detailed report on the postmortem distribution of thiamethoxam.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"356-362"},"PeriodicalIF":2.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From field prick to decision-grade proof: a dried blood spot and volumetric absorptive microsampling framework for verifying chemical-agent exposure.","authors":"M Vijayasimha","doi":"10.1007/s11419-026-00756-5","DOIUrl":"10.1007/s11419-026-00756-5","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"458-460"},"PeriodicalIF":2.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of fluvoxamine degradation products in postmortem blood by liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry.","authors":"Yoshikazu Yamagishi, Kazuaki Takahashi, Hiroyuki Inoue, Sayaka Nagasawa, Hirotaro Iwase, Yasumitsu Ogra","doi":"10.1007/s11419-026-00763-6","DOIUrl":"10.1007/s11419-026-00763-6","url":null,"abstract":"<p><p>PURPOSE: Fluvoxamine (FLV) is a selective serotonin reuptake inhibitor primarily used to treat obsessive-compulsive disorder. In Japan, FLV is linked to lethal intoxication and suicide cases. Therefore, it is important to establish its exact concentration in postmortem (PM) blood. It has been reported that blood FLV concentration decreases over time. In this study, we aimed to clarify the mechanisms underlying changes in FLV concentration in human blood over time. METHODS: We examined whether FLV underwent hydroxylation and/or oxidation in a Fenton reaction mixture containing FeCl2, hemoglobin (Hb), or hydrogen peroxide (H2O2) after incubating at 37 °C for 24 h. In addition, we measured FLV and its degradation products in human blood by liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry. RESULTS: Mass spectrometric result indicated the formation of (E)-N-(2-(((5-methoxy-1-(4(trifluoromethyl)phenyl)pentylidene)amino)oxy)ethyl)formamide (FLV-CHO), (E)-5-hydroxy-1-(4-(trifluoromethyl)phenyl)pentan-1-one-O-(2-aminoethyl)oxime (FLD), and (E)-5-(hydroxymethoxy)-1-(4-(trifluoromethyl)phenyl)pentan-1-one-O-(2-aminoethyl)-oxime (FLV-OH) in the reaction mixture. In addition, FLV-CHO concentration in human blood was strongly correlated with percentage FLV degradation relative to its initial concentration. CONCLUSIONS: Our results indicate that FLV-CHO, formed by Hb/H2O2-mediated FLV degradation in blood, is a potential biomarker for correcting FLV concentration in PM blood.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"349-355"},"PeriodicalIF":2.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13303306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Employing quantitative nuclear magnetic resonance for reliable forensic drug testing.","authors":"Taichi Nishihori, Miyu Ueki, Haruhi Yoshida, Haruyasu Asahara, Tsuyoshi Inoue, Hiroshi Matsumoto, Kazuo Harada","doi":"10.1007/s11419-026-00760-9","DOIUrl":"10.1007/s11419-026-00760-9","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"452-457"},"PeriodicalIF":2.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}