Forensic Toxicology最新文献

{"title":"Pharmacokinetic interaction between ketamine and ethanol: evaluation and forensic implications.","authors":"Jin Ah Won, Jeong In Seo, Yejin Kim, Sooyeun Lee, Hye Hyun Yoo","doi":"10.1007/s11419-026-00788-x","DOIUrl":"https://doi.org/10.1007/s11419-026-00788-x","url":null,"abstract":"<p><strong>Purpose: </strong>Ketamine (KET) is a psychoactive compound used medically but often misused in ethanol (EtOH)-facilitated sexual assault (EFSA), posing serious forensic challenges. Because EtOH may alter KET absorption and metabolism, understanding their pharmacokinetic interaction is critical for accurate toxicological interpretation in EFSA cases. This study aimed to evaluate the potential pharmacokinetic interactions between KET and EtOH through in vitro metabolism studies and in vivo rat experiments.</p><p><strong>Method: </strong>Prior to evaluating the PK interaction, in vitro metabolism studies were conducted using human and rat liver microsomes to identify the major circulating metabolites of KET. To assess the effects of EtOH on KET metabolism and disposition, KET (30 mg/kg) and EtOH (2 g/kg, 30%) were orally co-administered to rats, and blood and urine samples were collected over time. The plasma concentrations and urinary excretion of KET and its metabolites were analyzed using liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>Metabolism profiling study confirmed that KET undergoes sequential oxidative and conjugative metabolism, primarily forming norketamine (NK) and hydroxynorketamine (HNK) as major metabolites, along with dehydronorketamine (DHNK) and HNK-glucuronide (HNK-GLU) as minor ones. Pharmacokinetic studies showed that ethanol did not significantly alter plasma or urinary levels of KET, NK, or HNK. Accordingly, EtOH was not considered to have a significant impact on the KET PK and metabolism.</p><p><strong>Conclusions: </strong>This study provides experimental evidence that, under acute ethanol co-exposure conditions, no significant PK interaction between KET and EtOH was observed. These findings may help inform the interpretation of toxicological findings related to KET use in EFSA cases.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982492","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":"Emerging cannabinoids differ in behavioral safety margins in mice: a comparative hazard proximity analysis of locomotor suppression and catalepsy-like immobility.","authors":"Shintaro Shirakura, Arisa Ohta, Hiroko Abe, Kayo Nakamura, Akihiko Ishida, Manabu Tokeshi, Kyohei Higashi, Hideyo Takahashi, Akiyoshi Saitoh","doi":"10.1007/s11419-026-00786-z","DOIUrl":"https://doi.org/10.1007/s11419-026-00786-z","url":null,"abstract":"<p><strong>Purpose: </strong>Novel cannabinoids, including tetrahydrocannabihexol (THCH), tetrahydrocannabivarin (THCV), hexahydrocannabinol (HHC), hexahydrocannabihexol (HHCH), and hexahydrocannabiphorol (HHCP), have raised toxicological concerns, but their acute neurobehavioral effects remain poorly understood. This study compared the in vivo potencies of six cannabinoids using locomotor suppression and catalepsy-like immobility as indices of psychomotor suppression and toxic motor impairment, respectively.</p><p><strong>Methods: </strong>Male C57BL/6J mice received intraperitoneal administration of Δ9-tetrahydrocannabinol (THC), HHC, THCH, THCV, HHCH, or HHCP. Catalepsy-like immobility was assessed using the bar test 20 min after dosing (maximum latency, 300 s), and spontaneous locomotor activity was recorded for 10 min beginning 35 min after dosing. ED50 values were determined for locomotor suppression and catalepsy-like immobility, and the Hazard Proximity Index (HPI, %) was calculated as (ED50_locomotor / ED50_catalepsy) × 100, with higher values indicating a narrower behavioral safety margin.</p><p><strong>Results: </strong>All cannabinoids reduced spontaneous locomotor activity. THC, THCH, HHCH, and HHCP produced robust catalepsy-like immobility, whereas HHC induced only weak, non-significant immobility. THCV increased immobility only at higher doses and did not reach 50% catalepsy within the tested dose range. HPI values were 25.6% for THC, 45.1% for THCH, 5.1% for HHC, 33.2% for HHCH, and 3.7% for HHCP; HPI was not calculated for THCV.</p><p><strong>Conclusions: </strong>Psychomotor suppression occurred at lower doses than catalepsy-like toxicity. Some side-chain-extended cannabinoids, particularly THCH and HHCH, showed a narrower separation between these endpoints. These findings provide comparative ED50 benchmarks and introduce the HPI as a novel ED50-based screening metric for the relative prioritization of emerging cannabinoids in forensic toxicology.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967369","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":"p-Nitrophenoxy analogs as practical surrogates for Novichok-related biomarker verification in forensic toxicology.","authors":"Akinori Yamaguchi, Mai Otsuka, Takeshi Ohmori, Yuko Kazui, Hajime Miyaguchi","doi":"10.1007/s11419-026-00782-3","DOIUrl":"https://doi.org/10.1007/s11419-026-00782-3","url":null,"abstract":"<p><strong>Purpose: </strong>Authentic Novichok (A-series) nerve agents are highly restricted, making the rapid preparation of positive controls and reference materials challenging in forensic toxicology. This study aimed to evaluate p-nitrophenoxy analogs as surrogate compounds for Novichok-related biomarker verification by assessing their synthetic accessibility, ability to generate diagnostically relevant butyrylcholinesterase (BuChE) nonapeptide biomarkers, and functional relevance in cholinesterase inhibition and reactivation assays.</p><p><strong>Methods: </strong>Six surrogate compounds representing phosphate- and phosphonate-type analogs were prepared using a revised synthetic sequence with scaffold-dependent optimization of the reaction and purification conditions. Their utility was evaluated using plasma BuChE inhibition assays, 2-pyridine aldoxime methochloride (2-PAM)-mediated reactivation studies, inhibition kinetics with horse BuChE and human acetylcholinesterase, and liquid chromatography-tandem mass spectrometry analysis of BuChE-derived nonapeptide adducts in plasma. Operational applicability was examined using the OPCW biomedical proficiency test (BioPT) evaluation criteria.</p><p><strong>Results: </strong>All six surrogate compounds were obtained by structural class-dependent optimizations of their synthesis and purification. The plasma BuChE IC₅₀ values of authentic A230, A232, A234, A242, A262, and A2xx were 12.3, 9.6, 8.6, 10.1, 10.6, and 24.5 ng/mL, respectively, whereas those of the corresponding surrogates were 58.5, 38.6, 55.2, 3942, 3829, and 2575 ng/mL. 2-PAM-mediated BuChE reactivation showed similar qualitative patterns within each authentic/surrogate pair. All surrogates generated analytically equivalent BuChE nonapeptides and could be used to prepare qualitative reference materials for the OPCW BioPT-related workflow.</p><p><strong>Conclusion: </strong>p-Nitrophenoxy Novichok-related analogs provide a practical surrogate platform for preparing diagnostically relevant BuChE nonapeptide reference materials without using authentic A-series nerve agents.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918861","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":"Utility of tissue as an alternative specimen to blood for measuring volatile hydrocarbon concentrations in fire-related-deaths.","authors":"Ryota Hiraiwa, Ako Sasao, Kosei Yonemitsu, Kyoko Hirata, Yuki Ohtsu, Hiroshi Tsutsumi, Satoko Kimura, Shota Furukawa, Yoko Nishitani, Rie Sano","doi":"10.1007/s11419-026-00783-2","DOIUrl":"https://doi.org/10.1007/s11419-026-00783-2","url":null,"abstract":"<p><strong>Purpose: </strong>Quantitative analysis of volatile hydrocarbons (VHCs) in postmortem blood provides insight into the circumstances of fire-related deaths. Detection of specific VHCs can distinguish construction fires from those involving gasoline or kerosene. Although VHC concentrations have been examined in heart blood, their concentrations in other specimens remain unclear. We evaluated the correlations of carboxyhemoglobin and VHC concentrations among heart blood and femoral vein blood or various organ tissues to investigate the viability of alternative specimens for cases where heart blood cannot be collected.</p><p><strong>Methods: </strong>Heart blood, femoral vein blood, brain, liver, and muscle samples were collected from victims of fire-related death cases processed at our department. Seventeen VHCs were analyzed using headspace gas chromatography-mass spectrometry.</p><p><strong>Results: </strong>In construction fire cases, carboxyhemoglobin concentrations in heart blood were positively correlated with those in femoral vein blood. Benzene, toluene, and styrene are commonly detected in fire-related deaths, and the concentrations of these compounds in heart blood were positively correlated with the corresponding concentrations in femoral vein blood. The concentrations in heart blood were significantly higher than those in femoral vein blood. Tissue concentrations were also positively correlated with those in heart blood. Among the samples, brain tissue had the highest concentrations. In gasoline- and kerosene-related fire cases, the VHC concentration patterns in the brain were similar to those observed in heart blood.</p><p><strong>Conclusions: </strong>These results suggest that brain tissue is an appropriate specimen for VHCs analysis and can be used when VHCs are undetectable in heart blood or heart blood is not available.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911380","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":"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}