{"title":"The identification of N-isopropyl butylone in postmortem cases in Northern Virginia.","authors":"Ashley Pluer, Travon Cooman, Meghan Kessler","doi":"10.1093/jat/bkag037","DOIUrl":"10.1093/jat/bkag037","url":null,"abstract":"<p><p>The emergence of synthetic cathinones in the illicit drug market over the past two decades has posed significant challenges for forensic laboratories. Marketed initially as \"legal highs,\" these stimulants rose in popularity around 2009, prompting the United States government to pass the Synthetic Drug Abuse Prevention Act in 2012. Despite regulatory measures, novel cathinones continue to surface in forensic casework. One such compound is N-isopropyl butylone, a structural isomer of N, N-dimethylpentylone-the most frequently identified synthetic cathinone in 2023 in the United States. Detected by the Virginia Department of Forensic Science in March 2024, N-isopropyl butylone has since appeared in items including solid material, powders, tablets, crystalline material, and residues in 170 Controlled Substances cases across the Commonwealth through July 2025. From July to September 2024, the Northern Laboratory's Toxicology Section presumptively identified the compound in six postmortem blood specimens with detection in an additional blood specimen in August 2025. This study investigates the seven toxicology cases, with three being selected for further research analysis. Cases were assessed for case history, additional toxicology findings, and cause/manner of death. Presumptive positive identifications were made using full-scan gas chromatography-mass spectrometry. Confirmation and semi-quantitative analysis utilized an adapted stimulant-targeted extraction with liquid chromatography-tandem mass spectrometry. N-Isopropyl butylone was confirmed in three cases at semi-quantitative values of 20, 200, and 1700 ng/mL. All seven cases involved poly-drug use with four deaths being attributed to drug intoxication and three to fatal gunshot wounds. Although N-isopropyl butylone has only been observed in seven postmortem Toxicology cases, its increased prevalence in Controlled Substances cases could indicate broader circulation. These findings highlight the growing concern over novel psychoactive substances and the need for continued surveillance and research to assess their role in forensic casework.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential for postmortem formation of ethanol in vitreous humor.","authors":"Brianna L Peterson, Kari M Midthun, Laura M Labay","doi":"10.1093/jat/bkag044","DOIUrl":"10.1093/jat/bkag044","url":null,"abstract":"<p><p>Interpretation of ethanol results in postmortem blood samples has well-known limitations. After death, ethanol can form in the blood if sufficient glucose and microorganisms are present to facilitate the fermentation process. The potential for postmortem formation of ethanol has led to the widespread practice of verifying blood ethanol concentrations in a secondary matrix, typically vitreous humor when available. This study examined underlying trends and causes of postmortem ethanol formation in vitreous humor. Postmortem casework from 1 January 2022 to 31 December 2024 was investigated for cases where ethanol was reported in vitreous humor but not detected in a paired blood sample. Volatile analysis was performed by headspace gas chromatography on dual columns with flame ionization detectors. Ethanol, methanol, isopropanol, and acetone were screened in both blood and vitreous humor at reporting limits of 10, 10, 5.0, and 5.0 mg/dL, respectively. During this timeframe, 858 cases were identified with vitreous humor ethanol concentrations ranging from 10 to 624 mg/dL (mean 49 mg/dL, median 20 mg/dL). Of those identified, 683 cases (79%) had low-range vitreous ethanol concentrations (10-49 mg/dL). Possible biomarkers of ketoacidosis were also assessed in the 858 cases, with 464 cases (54%) reporting positive acetone and/or isopropanol. Additionally, elevated levels of beta-hydroxybutyric acid (BHB) (≥ 250 µg/mL) in either the blood or vitreous humor, were detected in 92% of cases (n = 140) tested for BHB; elevated levels of glucose (≥ 200 mg/dL) in vitreous humor were detected in 37% of cases (n = 458) tested for glucose. The results of this study highlight the importance of testing multiple matrices for ethanol in postmortem casework and the potential for postmortem ethanol formation in unpreserved specimens.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differential addictive potential of cis- and trans-3-methylfentanyl revealed by pharmacokinetic-pharmacodynamic profiling.","authors":"Xin Bai, Yao Chen, Zi-Qing Wei, Jing Bian, Chuan-Ming Zhou, Li-Hong Lv, Hui Zheng, Yan-Biao Zhao, Yu-Lan Rao, Zhi-Ru Xu","doi":"10.1093/jat/bkag049","DOIUrl":"10.1093/jat/bkag049","url":null,"abstract":"<p><p>3-Methylfentanyl (3-MF) is a highly potent synthetic opioid linked to a high risk of overdose. Although its analgesic effects are known to be stereoselective, the differences in addictive potential between its cis- and trans-isomers have not been fully elucidated. This study aimed to compare the abuse liability of cis- and trans-3-MF isomers using behavioral, pharmacokinetic, neurochemical, and transporter-based evaluations in rodents. Conditioned place preference (CPP) was used to assess addiction potential in rodents. Pharmacokinetic profiles were evaluated in rats via intravenous (iv), intramuscular (im), and subcutaneous (sc) routes. Brain microdialysis measured nucleus accumbens (NAc) exposure and monoamine release. In vitro transporter assays assessed interactions with breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). Cis-3-MF induced CPP at 8-fold lower doses than trans-3-MF (10 vs. 80 µg/kg). Pharmacokinetic analyzes revealed that trans-3-MF had higher plasma exposure after intravenous administration, while cis-3-MF showed nearly 100% bioavailability via intramuscular or subcutaneous routes. Microdialysis demonstrated 2.7-fold greater nucleus accumbens exposure of cis-3-MF and a more rapid and pronounced DA release (Cmax: 67 vs. 37 ng/ml for trans-3-MF). In contrast, trans-3-MF induced a slower increase in DA but elevated 5-HT levels. Trans-3-MF was identified as a partial BCRP substrate, potentially limiting brain penetration. Neither isomer interacted significantly with P-gp. Stereochemistry critically influences the addictive potential of 3-MF isomers. Cis-3-MF demonstrates greater abuse liability, driven by enhanced brain exposure and dopaminergic activation. These findings contribute to understanding stereoselective risks in synthetic opioid toxicity and support improved safety evaluations for novel analogs.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Munchelou M Gomonit, Gunnel H Nilsson, Ingrid Nyström, Liselotte Berglund, Fredrik C Kugelberg, Maria D Chermá, Johan Ahlner, Michael T Truver, Robert Kronstrand
{"title":"Blood pharmacokinetics and use of metabolite-to-parent ratios to predict time of last zopiclone intake.","authors":"Munchelou M Gomonit, Gunnel H Nilsson, Ingrid Nyström, Liselotte Berglund, Fredrik C Kugelberg, Maria D Chermá, Johan Ahlner, Michael T Truver, Robert Kronstrand","doi":"10.1093/jat/bkag032","DOIUrl":"10.1093/jat/bkag032","url":null,"abstract":"<p><p>Zopiclone (ZOP) is a sedative-hypnotic drug that is featured commonly in impaired driving, drug-facilitated crimes, accidental overdose, or suicidal intoxications. Further understanding of its blood pharmacokinetics would support its interpretation in forensic toxicology casework. This study characterizes the concentration-time pharmacokinetic profiles of ZOP and its metabolite N-desmethylzopiclone (N-DMZOP) in blood following controlled administration and evaluates the use of metabolite-to-parent ratios in estimating time of last ZOP intake. Sixteen subjects received a single oral dose of either 5 mg or 10 mg Imovane®, and blood samples were collected pre-dosing, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 24, and 48 hours post-dose. A paired plasma sample was also provided at the 2-hour time point. A previously validated LC-MS/MS method was used to quantify ZOP, N-DMZOP, and the degradation product 2-amino-5-chloropyridine (ACP). The aggregate regression model developed from this younger subject population was applied to independently dosed subjects and a separate group of elderly patients to determine the validity of this model in an older cohort of differing pharmacokinetic characteristics. Comparison between the 5 mg and 10 mg dosing groups supported a linear dose-concentration relationship. While the ratio of N-DMZOP/ZOP can be a predictive indicator for time of ZOP intake, inter-individual differences in ZOP disposition may influence such predictions. Furthermore, age-related pharmacokinetic changes may contribute to a general underestimation of predicted time with the current model, but a larger sample size of a broader demographic spectrum and dosing regimen would help improve the general applicability of this ratio-based modeling. Finally, we show that the mean blood-to-plasma ratio for ZOP and N-DMZOP were 0.79 and 0.92, respectively, suggesting a preferential partitioning of ZOP into the plasma fraction, which would be a useful reference when interpreting plasma concentrations from clinical studies against the more routinely sampled whole blood concentrations found in forensic toxicological casework.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brigitte Desharnais, Jocelyn V Abonamah, Szabolcs Sofalvi, Pascal Mireault
{"title":"Achieving a more accurate method of standard addition through mathematical improvements.","authors":"Brigitte Desharnais, Jocelyn V Abonamah, Szabolcs Sofalvi, Pascal Mireault","doi":"10.1093/jat/bkag047","DOIUrl":"10.1093/jat/bkag047","url":null,"abstract":"<p><p>The method of standard addition (MSA) has recently benefited from a popularity boost. In this approach, aliquots from a sample with an unknown analyte concentration are spiked with increasing analyte amounts. When plotting the measured signals against the spiked concentrations, the absolute value of the x-axis intercept is the unknown's concentration. Unfortunately, guidance on the best practices for performing MSA is extremely slim. In this article, we rely on literature, mathematical theory, and in silico simulations to build a framework for optimal accuracy when implementing the MSA approach. Our recommendations are as follows. (i) The highest upspike concentration should be as high as possible without saturating the detector; at least five times the estimated unknown concentration is a good rule of thumb. (ii) Adding measurement replicates should be favored over adding new upspike concentrations. (iii) Upspikes towards the low end of the dynamic range should be favored, insofar as their signal is differentiable from the unknown. (iv) To simplify calculations, coordinate swapping should be performed; i.e. signal measurements (e.g. area, area ratio) are recorded as the x values and spiked concentrations as the y values. (v) In performing the least squares regression, weight is set to 1/variance if three or more replicates are available, otherwise, to 1/(signal)2. (vi) If the confidence interval of the quadratic (b2) parameter includes zero, then a linear model should be used for the regression. Otherwise, a quadratic model should be used. (vii) Measurement uncertainty should be calculated using uncertainty contributors uCRM (uncertainty contributed by the certified reference material, as stated on its certificate of analysis) and uMSA (uncertainty contributed by the MSA procedure, which is the uncertainty of the y-intercept, ub0, when using a coordinate-flipped framework).</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Analysis of suzetrigine, a novel nonopioid pain medication, in whole blood and urine using liquid chromatography-tandem mass spectrometry.","authors":"Isabelle R Parry, Britni N Skillman","doi":"10.1093/jat/bkag041","DOIUrl":"10.1093/jat/bkag041","url":null,"abstract":"<p><p>Suzetrigine (JOURNAVX®) is a novel non-opioid pain medication that was approved in January 2025. Given the well-documented abuse potential of opioids, suzetrigine may become more widely prescribed as an alternative for acute pain management. However, it could still appear in forensic casework as little is understood about its role in polydrug toxicity, comorbidity with pre-existing health conditions, or abuse potential within larger populations. As such, this research aimed to develop the first forensically focused method to detect suzetrigine in blood and urine. Due to its similar physicochemical properties, suzetrigine was seamlessly integrated into a previously validated liquid-liquid extraction method developed for novel dual orexin receptor antagonists (DORAs). This report focuses on the subsequent method development and validation for suzetrigine detection using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated in accordance with ANSI/ASB 036 for the quantification of suzetrigine in blood and its qualitative identification in urine. A quadratic calibration model with 1/x weighing was utilized (1.0-1000 ng/ml) with quality controls (QCs) at 1.5, 80, 400, and 800 ng/ml. The limit of detection in blood and urine was 0.25 ng/ml, while the limit of quantitation in blood was 1.0 ng/ml. Post-extraction addition at 5 and 500 ng/ml yielded matrix effects less than ±25%, but increased variability at the low concentration in blood was deemed to have no impact on LOD. No carryover or interferences were observed from the internal standard, matrices, or common drugs. Dilution integrity (5X) was acceptable in blood, and processed samples were stable up to 72 hours in the autosampler. In this report we describe a simple extraction for suzetrigine in blood and urine followed by LC-MS/MS analysis. This analytical workflow will be valuable as the use of suzetrigine becomes more prevalent in casework samples.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marilyn A Huestis, Martin A Brett, John Bothmer, Jack E Henningfield, Sibyl Swift
{"title":"Mitragynine and 7-hydroxy-mitragyine plasma pharmacokinetics in humans after single and 15 multiple oral kratom extract doses.","authors":"Marilyn A Huestis, Martin A Brett, John Bothmer, Jack E Henningfield, Sibyl Swift","doi":"10.1093/jat/bkag042","DOIUrl":"10.1093/jat/bkag042","url":null,"abstract":"<p><p>Kratom, a medicinal Southeast Asian plant, gained interest in the United States for its analgesic and stimulant effects. Previous clinical studies characterized mitragynine and 7-hydroxy-mitragynine (7-OH-MTG) plasma pharmacokinetics following kratom tea and dried kratom leaf powder intake; however, to date, there are no kratom extract data. In the current study, mitragynine and 7-OH-MTG plasma pharmacokinetics are characterized in humans following increasing single doses (SD) and 15 multiple daily doses (MD) of concentrated kratom extract (39.5% mitragynine) containing 9.9, 29.6, and 59.2 mg mitragynine. Mean mitragynine plasma Cmax after single escalating doses increased dose-dependently, 32.8 ± 17.0, 93.2 ± 38.6, and 196 ± 77.4 ng/ml at a median Tmax of 1.3 h, with mean 7-OH-MTG Cmax of 6.8 ± 2.7, 13.7 ± 3.3, and 30.5 ± 12.2 ng/mL at a median Tmax of 1.3-1.7 h. Mean mitragynine plasma Cmax after 15 escalating multiple doses increased dose-dependently, 27.4 ± 10.9, 125 ± 79.7, and 277 ± 48.8 ng/mL at a median Tmax of 1.7-2.0 h, with mean 7-OH-MTG Cmax of 5.4 ± 1.9, 16.6 ± 6.1, and 33.9 ± 5.5 ng/mL at a median Tmax of 1.7-2.3 h. Cmax and AUC increased dose-dependently following SD and MD but were less than 1.4X greater than expected for both analytes and all doses based on strict dose proportionality. Half-lives were best reflected at higher doses due to the ability to measure low analyte concentrations longer but also suggested possible enzyme saturation. Higher 7-OH-MTG to mitragynine ratios were observed after multiple doses compared to SD and at lower compared to higher doses. These data indicate that concentrated kratom extracts may yield greater overall mitragynine exposure than dried kratom leaf powder or kratom tea preparations administered at comparable doses.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pirkko Kriikku, Paula Vauhkonen, Ilkka Ojanperä, Petteri Oura
{"title":"Theory put into practice: probabilistic approach to propranolol as the cause of death.","authors":"Pirkko Kriikku, Paula Vauhkonen, Ilkka Ojanperä, Petteri Oura","doi":"10.1093/jat/bkag059","DOIUrl":"10.1093/jat/bkag059","url":null,"abstract":"<p><p>Post-mortem forensic toxicology aims to assist in cause-of-death investigations, especially in suspected toxicity cases. Utilizing a large toxicology database derived from routine medico-legal autopsies, we tested a probabilistic approach in assessing the contribution of a toxicological finding to the underlying cause of death. In this retrospective study, theoretical general prior odds for a poisoning death were calculated for three different groups of cases based on the laboratory referral issued by the forensic pathologist. The groups were, in descending order according to the likelihood of poisoning: (i) suspected poisoning (N = 6356), (ii) exclusion of poisoning (N = 12 641), and (iii) for background information only (N = 15 018). Propranolol was selected as a model compound with 548 propranolol-positive cases in the database. First, the detected propranolol concentrations were divided into concentration ranges. Then, a likelihood ratio (LR) for each concentration range was calculated as the probability of observing a propranolol concentration within a certain concentration range given that propranolol poisoning was the cause of death, divided by the probability of observing a propranolol concentration within the same concentration range given that propranolol poisoning was not the cause of death. To showcase the practical applicability, posterior odds for fatal propranolol poisoning were derived using the odds form of Bayes' theorem (posterior odds = prior odds × LR) for a selection of propranolol-positive cases (N = 5) and compared with the cause of death recorded on the death certificate. In our dataset, the point estimate for LR exceeded 1 for propranolol concentrations ≥1.0 mg/L. The LR proved useful in assisting in the cause-of-death determination and making the interpretive process more systematic and transparent. Despite some limitations, this study added to the evidence of the usefulness of a probabilistic approach in assessing the relevance of a toxicology finding in autopsy cases.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Postmortem redistribution and quantitative analysis of bromazolam, etizolam, flualprazolam, and flubromazolam.","authors":"Elisa N Shoff, Joseph H Kahl, Diane M Moore","doi":"10.1093/jat/bkag033","DOIUrl":"10.1093/jat/bkag033","url":null,"abstract":"<p><p>Novel Psychoactive Substances (NPS) have been consistently prevalent in postmortem casework at the Miami-Dade County Medical Examiner (MDME) for over a decade. Between May 2019 and September 2025, 88 positive identifications of NPS benzodiazepines were reported, including bromazolam (n=47), etizolam (n=25), flualprazolam (n=15), and flubromazolam (n=1). To improve interpretation of these findings, a quantitative method for these four analytes was developed and fully validated for postmortem blood and tissues utilizing solid phase extraction followed by ultra-high performance liquid chromatography-tandem mass spectrometry. Postmortem redistribution (PMR) was also evaluated for each analyte. In total, 180 specimens from 81 cases were analyzed, including 70 peripheral bloods, 72 central bloods, 18 liver homogenates, 16 brain homogenates, and 4 antemortem bloods. Peripheral blood concentrations for bromazolam (n=26) and etizolam (n=14) ranged from 2.5-168 ng/mL (mean: 33.4 ng/mL; median: 16.9 ng/mL), and 2.3-350 ng/mL (mean: 59.4 ng/mL; median: 12.1 ng/mL), respectively. Central blood concentrations for bromazolam (n=27) and etizolam (n=15) ranged from 3.0-153 ng/mL (mean: 38.3 ng/mL; median: 17.6 ng/mL), and 2.0-295 ng/mL (mean: 67.5 ng/mL; median: 15.3 ng/mL), respectively. Flualprazolam concentrations were notably lower with peripheral blood (n=3) concentrations ranging from 2.2-9.0 ng/mL (mean: 5.6 ng/mL; median: 5.7 ng/mL), and central blood (n=5) concentrations ranging from 2.4-10.6 ng/mL (mean: 6.0 ng/mL; median: 6.5 ng/mL). PMR ratios were calculated for central to peripheral blood (C/P), liver to peripheral blood (L/P), liver to central blood (L/C) and postmortem to antemortem blood (PM/AM). Median C/P and PM/AM ratios were ≤1.3, while median L/P ratios were ≤5.2. The observed PMR ratios are comparable to those reported for traditional benzodiazepines, suggesting limited PMR. The observed C/P ratios further suggest that central blood may be suitable for quantitative interpretation when peripheral blood is unavailable. This study represents the first systematic evaluation of C/P, L/P, L/C, and PM/AM ratios for NPS benzodiazepines across multiple cases.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on Deeb et al.: interpretation of breath cannabinoids and implications for impairment.","authors":"Aaron Olson","doi":"10.1093/jat/bkag028","DOIUrl":"10.1093/jat/bkag028","url":null,"abstract":"<p><p>This letter addresses the article by Deeb et al. describing the analysis of cannabinoids in exhaled breath. While the study represents a technical advancement in breath-based detection, several interpretive and analytical limitations warrant clarification. The manuscript discusses potential impairment-related applications despite the absence of direct measures of impairment. Existing literature, including controlled clinical studies and government reports, indicates that THC concentrations in biological matrices cannot be used as a reliable indicator of impairment. Additionally, key variables influencing cannabinoid exposure, including dose, potency, and inhalation behavior, were not controlled, further limiting interpretability. Analytical concerns are also noted, including subpar chromatographic resolution (Rs ≈ 0.9), which may compromise accurate identification and quantitation of structurally similar cannabinoids. These issues highlight the need for caution in interpreting breath cannabinoid data, particularly in forensic contexts where conclusions regarding impairment may carry significant consequences.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13234941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}