Forensic Toxicology最新文献

{"title":"Quantitative analysis of stimulants in whole blood using an evaporation free precipitation salt assisted liquid-liquid extraction (SALLE) sample preparation approach.","authors":"Jon Stephenson, Joseph Austin, Bailey Carney, Melanie Flater, Skye Mullarkey, Michael Morrison","doi":"10.1007/s11419-025-00724-5","DOIUrl":"10.1007/s11419-025-00724-5","url":null,"abstract":"<p><strong>Purpose: </strong>The increasing prevalence of methamphetamine and cocaine in postmortem toxicology casework has placed significant demands on forensic laboratories. This study introduces and validates a streamlined method using salt assisted liquid-liquid extraction (SALLE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to improve the efficiency and reliability of detecting amphetamine-type stimulants (ATS) and cocaine metabolites in forensic toxicology.</p><p><strong>Methods: </strong>A new SALLE method was developed to analyze a panel of drugs, including amphetamine, methamphetamine, phentermine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), pseudoephedrine, cocaine, cocaethylene, and benzoylecgonine (BZE). Calibration models, bias, precision, recovery, matrix effects, interferences, limits of detection (LOD) and quantitation (LOQ), dilution integrity, carryover, and sample stability were evaluated following AAFS standard 036 guidelines. The method was applied to over 150 postmortem and human performance toxicology cases and compared with the traditional gas chromatography-mass spectrometry (GC/MS) approach.</p><p><strong>Results: </strong>The SALLE-LC-MS/MS method exhibited high accuracy, with all analytes meeting bias and precision criteria (< 20%). Percent recovery values exceeded 80%, while matrix effect values (ion suppression/enhancement) remained below 20%. LODs ranged from 5-25 µg/L, and LOQs ranged from 10-50 µg/L across analytes. Processed samples were stable for up to 8 days. Analysis of 150 cases showed strong agreement with the GC/MS method, with average percent differences ranging from 5.4 to 19.4% for most analytes. The new method reduced sample preparation time by 67% and data-processing time by 80%, resulting in overall time savings of 8 h per batch.</p><p><strong>Conclusions: </strong>The resulting validated SALLE procedure represents a significant advancement in the analysis of stimulant drugs within forensic toxicology. Its adoption at the Georgia Bureau of Investigation not only addresses current analytical challenges but also sets a precedent for the development of more efficient and reliable methods in the field.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"377-384"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474428","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":"Beware of misattributing 'modafinil' in diphenhydramine-positive cases.","authors":"Karolina Nowak, Marcin Zawadzki, Paweł Szpot","doi":"10.1007/s11419-025-00716-5","DOIUrl":"10.1007/s11419-025-00716-5","url":null,"abstract":"<p><strong>Purpose: </strong>Diphenhydramine is an antihistaminic agent available in numerous over-the-counter preparations, while modafinil is a wakefulness-promoting agent, available only by prescription, but also used recreationally, when purchased from the black market. Structurally, both substances belong to the class of so-called benzhydryl compounds, which can complicate their proper differentiation. The authors point out the possibility of misattributing modafinil in diphenhydramine-positive cases due to the likely coelution of nordiphenhydramine and modafinil.</p><p><strong>Methods: </strong>Post-mortem blood and vitreous humor samples were subjected to liquid-liquid extraction using ethyl acetate in an alkaline environment (pH = 9), followed by a detailed toxicological analysis utilizing ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry.</p><p><strong>Results: </strong>Through the application of full scan mode, multiple reaction monitoring (MRM), and product ion scan mode, the presence of modafinil was excluded in diphenhydramine-positive biological matrices (blood and vitreous humor).</p><p><strong>Conclusions: </strong>In the analysis of benzhydryl compounds, particular caution should be exercised, with each case verified by comparison with a certified analytical standard, and, where possible, by detecting the metabolites of these compounds.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"349-355"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751937","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":"GC/MS-based quantitative analysis of sulfide ion in whole blood using ethenesulfonyl fluoride as a derivatization reagent.","authors":"Ryosuke Shiraki, Shin Ogawa, Kengo Wakigawa, Hidehiko Okazaki, Akinaga Gohda, Takeshi Mori, Yoshiki Katayama","doi":"10.1007/s11419-025-00712-9","DOIUrl":"10.1007/s11419-025-00712-9","url":null,"abstract":"<p><strong>Purpose: </strong>Identification and quantification of sulfide ion in biological samples are required in forensic purpose. Gas chromatography-mass spectrometry (GC/MS) has been used for the analysis of sulfide ion by using derivatization reagents. However, conventional derivatization reagents require special attention for derivatization. To simplify the derivatization protocol, we examined ethenesulfonyl fluoride (ESF) as a derivatizing reagent of sulfide ion.</p><p><strong>Methods: </strong>To 100 μL of whole blood sample containing sulfide ion, 100 μL of boric acid buffer (pH 8.0), 100 μL of acetone solution containing internal standard, 100 μL of acetone solution containing 600 mM concentration of ESF, and 100 μL of hexane were added in a 1.5-mL plastic tube. The mixture was vortexed at room temperature, the tubes were centrifuged, and the organic layer was injected into the GC/MS.</p><p><strong>Results: </strong>ESF exhibited higher reactivity toward sulfide ion than interfering compounds present in whole blood, allowing for selective derivatization. With the optimized protocol, the detection limit for sulfide ion was 0.01 μg/mL. The calibration curve showed good linearity (R² = 0.9999) in the range of 0.05-10.0 μg/mL, and the precision (% relative standard deviation) and the accuracy (% bias) were within ± 10% (intra- and inter-day).</p><p><strong>Conclusion: </strong>This GC/MS-based method is a valuable tool for forensic investigations and various analytical fields, offering reliable quantification of sulfide ion in whole blood.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"226-234"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382042","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":"Evaluation of dried blood spot sampling for verification of exposure to chemical threat agents.","authors":"Katie A Walker, Trinity K Rudd, Justin N Vignola, Thomas M McClymont, Noah D Roberts, Kevin Laitipaya, Robert C diTargiani","doi":"10.1007/s11419-025-00721-8","DOIUrl":"10.1007/s11419-025-00721-8","url":null,"abstract":"<p><strong>Purpose: </strong>Exposure to chemical threat agents (CTAs), including nerve agents, the vesicating agent sulfur mustard, and opioids, remains a significant threat to warfighter and civilian populations. Definitive analytical methods to verify exposure to CTAs require shipping refrigerated or frozen biomedical samples to reference laboratories for analysis. Logistical and financial burdens arise as the transport of biomedical samples is subject to strict restrictions and complex packaging, which, if done incorrectly, can lead to sample deterioration. The use of dried blood spot (DBS) sampling could provide operational improvements for collecting, storing, and shipping important forensic samples. Therefore, this effort focuses on developing DBS techniques with Mitra® 30-µL volumetric absorptive microsampling (VAMS®) devices for use in CTA exposure verification.</p><p><strong>Methods: </strong>VAMS® devices were loaded and dried with human whole blood that was exposed to the metabolites pinacolyl methylphosphonic acid (PMPA), ethyl methylphosphonic acid (EMPA), 1,1'sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE), norfentanyl, norcarfentanil, norsufentanil, and norlofentanil. Following extraction from the VAMS® devices, metabolites were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The methods were validated for performance by assessing sensitivity, precision, accuracy, and recovery.</p><p><strong>Results: </strong>These methods were sensitive to 1 ng/mL for SBMSE, 0.5 ng/mL for PMPA, EMPA, and norfentanyl; 0.1 ng/mL for norlofentanil, and 0.05 ng/mL for norsufentanil and norcarfentanil. All methods met acceptable precision and accuracy criteria with favorable recovery.</p><p><strong>Conclusions: </strong>These results demonstrated the utility of VAMS® in stabilizing human whole blood and show promise as an improved collection method for verification of exposure to various CTAs.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"280-293"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993321","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":"Evaluating the value of entomotoxicology in forensic toxicology casework using the first minipig model.","authors":"Olwen C Groth, Anaëlle Pi, Andres E Jensen, Frank Reckel, Jiri Hodecek, Abderrahmane Kori Yahia, Susan Rahaus, Martin H Villet, Matthias Graw","doi":"10.1007/s11419-025-00728-1","DOIUrl":"10.1007/s11419-025-00728-1","url":null,"abstract":"<p><strong>Purpose: </strong>A principal objective of forensic entomotoxicology is to apply insect specimens for post-mortem toxicological analysis. Successful identification of drugs in necrophagous insects may depend on pharmacokinetic processes occurring in larvae. We thus applied a model system involving Lucilia sericata (Meigen, 1826) (Diptera, Calliphoridae) to investigate pharmacokinetics of diazepam in larvae in vitro, followed by a field experiment with Göttingen Minipigs.</p><p><strong>Methods: </strong>Lucilia sericata larvae were fed one of four diazepam concentrations at constant temperature, sampled regularly, and analysed for diazepam and metabolites by liquid chromatography tandem mass spectrometry (LC-MS/MS). Two Göttingen Minipigs of 60 kg each were euthanised one hour after oral administration of 25 mg/kg diazepam and placed outdoors. While available, samples of peripheral blood, cardiac blood, liver, and fly larvae were collected over 70 days. Extracts from porcine samples and larvae were analysed by LC-MS/MS. Some larvae were bred to adulthood and identified morphologically together with 718 larvae.</p><p><strong>Results: </strong>Oxazepam was a primary metabolite of diazepam in L. sericata larvae. The most prevalent fly species on minipig carcasses were Lucilia caesar (Linnaeus, 1758) (Diptera, Calliphoridae) and Lucilia illustris (Meigen, 1826) (Diptera, Calliphoridae). Diazepam and metabolites were detected in all larval samples, even weeks after porcine samples were unacquirable due to post-mortem decomposition. Ratios of oxazepam and nordazepam to diazepam concentrations in larvae were significantly higher than in associated porcine samples, confirming metabolism in larvae.</p><p><strong>Conclusion: </strong>These findings are relevant to forensic casework, as there is potential for misinterpreting that the deceased consumed oxazepam or nordazepam rather than diazepam. This caution may also apply to other drugs that can form through metabolism in larvae.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"333-348"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149804","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":"Cross-reactivity of the epimers of 11-nor-9-carboxy-hexahydrocannabinol, metabolites of hexahydrocannabinol, with panel tests for urinary Δ⁹-tetrahydrocannabinol metabolites.","authors":"Kenji Tsujikawa, Yuki Okada, Hiroki Segawa, Tadashi Yamamuro, Kenji Kuwayama, Tatsuyuki Kanamori, Yuko T Iwata","doi":"10.1007/s11419-025-00717-4","DOIUrl":"10.1007/s11419-025-00717-4","url":null,"abstract":"<p><strong>Purpose: </strong>The epimers of 11-nor-9-carboxy-hexahydrocannabinol (HHC-COOH) have been identified as metabolites of hexahydrocannabinol (HHC) in human urine. Owing to the similarity of chemical structures to 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (Δ⁹-THC-COOH), a major urinary metabolite of Δ⁹-tetrahydrocannabinol (Δ⁹-THC), HHC-COOH may show cross-reactivity in panel tests for urinary Δ⁹-THC metabolites. The authors have evaluated the cross-reactivity of HHC-COOH epimers in three commercial panel tests.</p><p><strong>Methods: </strong>Human urine spiked with 9α- and 9β-HHC-COOH (final concentrations: 20-500 ng/mL) was subjected to three panel tests (Driven Flow THC L50, IVeX-Screen THC L50-S, and AccuSign THC) with a nominal cutoff concentration of 50 ng/mL for Δ⁹-THC-COOH. Additionally, an intact urine sample from an alleged HHC user was used.</p><p><strong>Results: </strong>The lowest concentrations judged as positive were 100-500 ng/mL for 9α-HHC-COOH and 50-100 ng/mL for 9β-HHC-COOH. Intact urine samples from an alleged HHC user, whose 9α-/9β-HHC-COOH concentrations (ng/mL) were < 4.0/25.5 before alkaline hydrolysis and 13.4/132.2 after alkaline hydrolysis, were positive for all three panel tests.</p><p><strong>Conclusions: </strong>Both epimers of HHC-COOH showed cross-reactivity in three panel tests. The reactivity of 9β-HHC-COOH was found to be higher than that of 9α-HHC-COOH. The urine test results from the alleged HHC user suggested that the acyl glucuronides of HHC-COOH also exhibited cross-reactivity. Users of panel tests for urinary Δ⁹-THC metabolites should pay attention to false positives potentially caused by HHC metabolites.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"365-369"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735739","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":"Enzymatic hydrolysis of ∆⁸-THC-O, ∆⁹-THC-O, 11-α-HHC-O, and 11-β-HHC-O by pooled human liver microsomes to generate ∆⁸-THC, ∆⁹-THC, 11-α-HHC, and 11-β-HHC.","authors":"Shuangli Zhao, Jorge Carlos Pineda García, Ren-Shi Li, Ruri Kikura-Hanajiri, Yosuke Demizu, Yoshitaka Tanaka, Yuji Ishii","doi":"10.1007/s11419-025-00719-2","DOIUrl":"10.1007/s11419-025-00719-2","url":null,"abstract":"<p><strong>Purpose: </strong>In recent years, analogues of ∆⁹-tetrahydrocannabinol (∆⁹-THC) have been widely distributed in Japan via the internet. Hexahydrocannabinol (HHC), synthesized by reducing THC, was controlled as a designated substance under the Pharmaceutical and Medical Device Act in Japan in 2022. However, other semi-synthetic cannabinoids, such as acetyl derivatives of THC and HHC, appeared soon. Herein, we examined whether the enzymatic hydrolysis of acetylated forms of ∆⁹-THC, ∆⁸-THC 11-α-HHC, and 11-β-HHC by human liver microsomes (HLM) occurs.</p><p><strong>Methods: </strong>The hydrolysis reaction was accomplished with HLM. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine products. Recombinant enzymes carboxylesterase 1C (CES1c), carboxylesterase 2 (CES2), and carboxylesterase inhibitor bis-(4-nitrophenyl) phosphate (BNPP) were used to clarify the principal hydrolysis enzymes for acetylated cannabinoids.</p><p><strong>Results: </strong>The acetylated form underwent hydrolysis with HLM time-dependently, with almost no acetylated product remaining after 60 min. Furthermore, results from LC-MS showed that only the deacetylated form was present after hydrolysis. Although hydrolysis did not occur when HLM was pre-incubated with the carboxylesterase inhibitor BNPP, it was observed when CES1c or CES2 was used for in vitro experiments.</p><p><strong>Conclusion: </strong>This is the first time that it is elucidated that ∆⁹-THC-O, ∆⁸-THC-O, 11-α-HHC-O, and 11-β-HHC-O are enzymatically hydrolyzed with HLM to produce ∆⁹-THC, ∆⁸-THC, 11-α-HHC, and 11-β-HHC, respectively. Our results also support that CES1c and CES2 were the main enzymes involved in the hydrolysis of the acetylated cannabinoids. This study provides scientific support for the metabolism of newly regulated acetylated cannabinoids to cause the parent compound in vivo.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"256-265"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735741","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":"Non-consensual administration of mifepristone for hidden abortion: a rare case of drug-facilitated crime.","authors":"Laurie Gheddar, Audrey Farrugia, Jean-Sébastien Raul, Pascal Kintz","doi":"10.1007/s11419-025-00723-6","DOIUrl":"10.1007/s11419-025-00723-6","url":null,"abstract":"<p><strong>Purpose: </strong>In this paper, the authors report a hidden administration of mifepristone, an antiprogestogen used in abortion procedure, by the boyfriend of a pregnant woman. After drinking an iced tea, the woman experienced pelvic cramps and then expulsed products of conception. Due to conflicts in the couple, she suspected a surreptitious administration of an abortion medicine and reported the fact to the police.</p><p><strong>Methods: </strong>Urine was collected 3 days after the event, while a strand of head hair was collected 1 month later. Urine and hair samples were tested for mifepristone using a liquid chromatography system coupled to tandem mass spectrometry. The limits of detection and quantification were 0.05 and 0.1 ng/mL for urine and 0.5 and 1 pg/mg for hair, respectively.</p><p><strong>Results: </strong>Urine and the hair segment corresponding to the period of the event were positive for mifepristone at 0.4 ng/mL and 1.4 pg/mg, respectively.</p><p><strong>Conclusion: </strong>The presence of mifepristone in both biological specimens demonstrates that the woman was exposed to the drug at the period of the event. The findings of this case make a valuable contribution to the literature, addressing an important gap regarding the concentrations found in biological matrices. There is a few data available in the literature, and these results help to expand knowledge on the subject.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"395-399"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960583","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":"Urinary excretion profiles of the orexin receptor antagonist suvorexant and its metabolites.","authors":"Misato Wada, Hiroe Kamata, Noriaki Shima, Atsushi Nitta, Hidenao Kakehashi, Shihoko Fujii, Shuntaro Matsuta, Tooru Kamata, Munehiro Katagi, Hiroshi Nishioka","doi":"10.1007/s11419-024-00706-z","DOIUrl":"10.1007/s11419-024-00706-z","url":null,"abstract":"<p><strong>Purpose: </strong>Suvorexant is an orexin receptor antagonist used in the treatment of insomnia. In this study, we investigated the urinary excretion profiles of suvorexant and its major metabolites, including conjugates, to obtain fundamental information for proving exposure to suvorexant in criminal cases.</p><p><strong>Methods: </strong>Urine specimens were collected from three subjects for maximum 168 h after a single oral ingestion of suvorexant (10 mg), and suvorexant and its metabolites in urine were determined using liquid chromatography-tandem mass spectrometry with a C18 semi-micro column.</p><p><strong>Results: </strong>The carboxylic and hydroxy metabolites (M4 and M9) were identified with authentic standards synthesized in our laboratory, and their glucuronides and other hydroxy metabolites (M8 and M10) were tentatively detected based on measured exact masses and product ion spectra of them. Suvorexant, M4 and M9 would be detectable for 20-34 h, 6-7 days and 42-61 h after intake, respectively. The quantitative results demonstrated that the molar ratios of accumulated amounts of M4 and M9 including their glucuronides excreted in urine to dose ranged about 2.6-6.2% and 0.37-0.51%, respectively, while that of the unchanged parent was much lower (0.011-0.013%). The ratios of the amount of glucuronide to the total amount of M4 and M9 excreted in urine was less than 10% and approximately 90%, respectively.</p><p><strong>Conclusions: </strong>The urinary excretion profiles indicated that M4 and M9 would be effective indicators for proving suvorexant intake, and M4 could be detected until one week after intake even without enzymatic hydrolysis (limit of detection: 0.05 ng/mL).</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"179-189"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853547","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":"Acute and subacute cardiovascular effects of synthetic cannabinoid JWH-018 in rat.","authors":"Onural Ozhan, Necip Ermis, Osman Celbis, Emine Samdanci, Semih Petekkaya, Mucahit Oruc, Ozcan Soylu, Pelin Koparir, Ahmet Acet, Hakan Parlakpinar","doi":"10.1007/s11419-025-00720-9","DOIUrl":"10.1007/s11419-025-00720-9","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the cardiovascular effects of the synthetic cannabinoid naphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-018) in rats. The research aims to evaluate the pharmacologic, cardiologic, biochemical, and histopathological effects of acute and subacute administration at low and high doses. The primary research question is how JWH-018 impacts heart function, blood pressure, ECG patterns, and cardiac tissue integrity.</p><p><strong>Methods: </strong>Wistar albino rats were divided into five groups: control, acute low-dose (ALD, 0.5 mg/kg), acute high-dose (AHD, 5 mg/kg), subacute low-dose (SALD, 0.5 mg/kg for 14 days), and subacute high-dose (SAHD, 5 mg/kg for 14 days). Cardiovascular effects were assessed using echocardiography, hemodynamic and ECG analysis, histopathology, biochemical markers, and LC-MS/MS quantification of JWH-018 and its metabolites in heart tissue.</p><p><strong>Results: </strong>Acute high-dose JWH-018 caused bradycardia and hypotension, while subacute high-dose increased heart rate but continued to lower blood pressure. JWH-018 induced cardiac arrhythmias, conduction blocks, and ischemic ECG changes, with prolonged QT intervals in subacute high-dose rats. Histopathological findings revealed myocardial infarction-like features, including contraction bands and ischemic damage, particularly in subacute groups. Elevated pro-BNP and triglycerides indicated cardiac stress and metabolic effects. JWH-018 and its metabolites were detected in heart tissue, primarily in high-dose groups.</p><p><strong>Conclusions: </strong>JWH-018 has significant cardiovascular risks, causing heart rate dysregulation, hypotension, arrhythmias, and ischemic damage. These effects depend on dose and duration. The study highlights the potential dangers of synthetic cannabinoids, emphasizing that they should not be considered safe alternatives to natural cannabis.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"266-279"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989740","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}