Forensic Toxicology最新文献

{"title":"Electromembrane extraction (EME)-LC-MS/MS of khat: improving separation and determination of bioactive ingredients in traditional plant and vitreous humor.","authors":"Aijia Zhang, Shuang Ye, Zilong Liu, Lingzhi Tan, Man Liang","doi":"10.1007/s11419-025-00726-3","DOIUrl":"https://doi.org/10.1007/s11419-025-00726-3","url":null,"abstract":"<p><strong>Purpose: </strong>Regional traditional plant khat, which have been recreationally used world-wide recently, has been proven to be a mixture of several biologically active ingredients. Herein, a chosen specimen, vitreous humor (VH) and a novel pretreatment, electromembrane extraction (EME), are applied for forensic investigations of such abused plant.</p><p><strong>Methods: </strong>VH, as an alternative matrix, is being used for evaluating possible compounds more and more; EME, a novel and efficient pretreatment method, is applied to detect the ingredients from natural complex matrices with advantages of a more sustainable microextraction technique. This study aims to analyze the ingredients of khat, norephedrine (NE), norpseudoephedrine (NPE) and cathinone (CTN), as well as their concentrations in VH of khat-treated mice applying EME.</p><p><strong>Results: </strong>After optimization, 2-ethylnitrobenzene (ENB)/undecanol was used as the support liquid membrane (SLM), HCl (pH = 2) as the acceptor solution, extraction voltage at 60 V, and extraction time for 30 min. The established EME was combined with liquid chromatography-ultraviolet spectrometry (LC-UV) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to evaluate spiked VH. The LOD of NE, NPE, and CTN were 0.40-1.90 µg/mL with linearity (R² > 0.9624) and repeatability (< 13%).</p><p><strong>Conclusions: </strong>By this method, NE, NPE, and CTN were detected to be 14.4 ± 0.54 µg/mL, 8.50 ± 0.69 µg/mL, and 90.5 ± 7.88 µg/mL in VH of mice administrated with khat for 28 days.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981530","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":"A simple method for the determination of stimulant substances in postmortem blood: development, validation, and application in nearly 1000 forensic cases.","authors":"Letícia Birk, Bruno Pereira Dos Santos, Daniela Souza Ossanes, Patrícia de Souza Schwarz, Mariana Lopes Mesquita, Sarah Eller, Tiago Franco de Oliveira","doi":"10.1007/s11419-025-00725-4","DOIUrl":"https://doi.org/10.1007/s11419-025-00725-4","url":null,"abstract":"<p><strong>Purpose: </strong>Toxicological analyses of postmortem blood samples are essential to elucidate forensic cases involving toxic agents, such as illicit drugs. A simple method for determining stimulant substances in postmortem blood samples through protein precipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and applied in nearly 1000 samples from Brazilian forensic cases.</p><p><strong>Methods: </strong>For sample preparation, 100 µL of postmortem blood was precipitated using acetonitrile. The supernatant was analyzed via LC-MS/MS system for sixteen substances, including amphetamine, benzoylecgonine, cocaethylene, cocaine, diethylpropion, dimethyltryptamine, ecgonine methyl ester (EME), ephedrine, fenproporex, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, 3,4-methylenedioxymethamphetamine, methamphetamine, methylphenidate, phenylephrine, and sibutramine. The method was validated following the parameters established by the ANSI/ASB Standard 036 Guideline. After validation, a total of 971 postmortem blood samples were analyzed.</p><p><strong>Results: </strong>The lower limits of quantification varied from 5 to 20 ng/mL, with all substances demonstrating linearity up to 1000 ng/mL. The method exhibited maximum precision values of 19.3%, while the bias ranged from - 15.4 to + 4.3%. A significant matrix effect was observed only for EME and phenylephrine. Approximately 20.1% of the analyzed samples tested positive for at least one substance, and 12 out of the 16 target analytes were detected. The most prevalent substances identified were benzoylecgonine (17.8%), ecgonine methyl ester (13.9%), and cocaine (13.0%).</p><p><strong>Conclusions: </strong>A rapid and straightforward LC-MS/MS method for the quantitative analysis of drugs in postmortem blood was validated and successfully applied to nearly 1000 postmortem blood samples.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005408","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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-19","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":"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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation of highly concentrated extracts from large volume of urine as the first step in detecting trace amounts of hypnotics in urine collected in drug-facilitated crime cases.","authors":"Kenji Kuwayama, Hajime Miyaguchi, Tatsuyuki Kanamori, Kenji Tsujikawa, Tadashi Yamamuro, Hiroki Segawa, Yuki Okada, Yuko T Iwata","doi":"10.1007/s11419-025-00722-7","DOIUrl":"https://doi.org/10.1007/s11419-025-00722-7","url":null,"abstract":"<p><strong>Purpose: </strong>Detecting hypnotics in victim urine samples collected several days after drug-facilitated crime (DFC) is challenging because most of the drugs have already been excreted. In this study, a sample preparation method was developed for extracting trace amounts of hypnotics using most of the urine excreted at one sampling time (100 mL), and large amounts of matrices were efficiently removed.</p><p><strong>Methods: </strong>Etizolam, midazolam, ramelteon, and their metabolites were used as the target compounds. As the first step in decreasing the sample volume, solid-phase extraction using various sorbents was examined. The effects of additional clean-up columns (alumina, graphite, anion exchanger, etc.) on the removal of urine matrices were also examined. The pretreatment of 0.1-mL urine using a simple extraction column, specialized for small-scale urinalysis (Isolute Hydro DME +), was used as the reference method. The feasibility of drug detection in 100-mL urine was evaluated by comparison with a reference method.</p><p><strong>Results: </strong>All analytes in 100-mL urine were most effectively adsorbed on a sorbent with octadecyl-bonded polymer and eluted with less than 2 mL of acetonitrile. A multilayer clean-up column consisting of alumina, octadecyl-bonded silica, and anion exchangers was effective in removing the matrices. α-Hydroxymidazolam was detected in 100 mL of urine that was collected 5 days after midazolam administration, but was undetected using the reference method.</p><p><strong>Conclusions: </strong>This preparation method for 100-mL urine is useful as the first extraction step in detecting trace amounts of hypnotics in victim urine collected late after DFC.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981916","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 two lysergic acid diethylamide analogs, 1-(3-(trimethylsilyl) propionyl) lysergic acid diethylamide (1S-LSD) and 1-(2-thienoyl)-6-allyl-nor-d-lysergic acid diethylamide (1T-AL-LAD), in paper sheet products distributed on the internet.","authors":"Rie Tanaka, Maiko Kawamura, Michiho Ito, Ruri Kikura-Hanajiri","doi":"10.1007/s11419-025-00718-3","DOIUrl":"https://doi.org/10.1007/s11419-025-00718-3","url":null,"abstract":"<p><strong>Purpose: </strong>Recently, numerous lysergic acid diethylamide (LSD) analogs have emerged as designer drugs globally. These compounds are mainly distributed as sheet products. In this study, two new LSD analogs were identified from sheet products.</p><p><strong>Methods: </strong>The structures of the compounds were determined by gas chromatography-mass spectrometry, liquid chromatography-photodiode array-mass spectrometry, liquid chromatography with hybrid quadrupole time-of-flight mass spectrometry and nuclear magnetic resonance (NMR) measurement.</p><p><strong>Results: </strong>From the NMR analysis, two compounds in the products were identified as N,N-diethyl-7-methyl-4-(3-(trimethylsilyl)propanoyl)-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1S-LSD) and 7-allyl-N,N-diethyl-4-(thiophene-2-carbonyl)-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1T-AL-LAD). In the product where 1S-LSD was detected, the presence of a trace amount of iso-1S-LSD, a C8-epimerization product of 1S-LSD, was suggested.</p><p><strong>Conclusions: </strong>This paper is the first to report the detection of 1S-LSD and 1T-AL-LAD in sheet products in Japan. Notably, the metabolic pathways and biological activities of 1S-LSD and 1T-AL-LAD are not explored. The possibility of the in vivo deacylation and conversion of the compoundsinto LSD or AL-LAD should be further investigated.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778992","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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","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":"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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","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":"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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","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}