Journal of analytical toxicology最新文献

{"title":"Hydroxyzine in Impaired Driving Investigations.","authors":"Jolene J Bierly, Amanda L D'Orazio","doi":"10.1093/jat/bkaf030","DOIUrl":"https://doi.org/10.1093/jat/bkaf030","url":null,"abstract":"<p><p>Hydroxyzine (Vistaril©) is an unscheduled, first-generation antihistamine prescribed for nausea/vomiting, atopic dermatitis or eczema, and anxiety. It can produce adverse central nervous system depressant (CNS) effects such as fatigue, sedation, and impaired memory and concentration. Several clinical studies have shown hydroxyzine is able to impair driving and psychomotor function; however, no case series have been published highlighting driving performance and roadside observations in driving under the influence of drugs investigations (DUID). Between January 2017 and October 2024, 319 blood specimens submitted for DUID testing confirmed positive for hydroxyzine. Mean and median blood concentrations were 70 ±79 ng/mL and 48 ng/mL respectively, with a range of 8.0-600 ng/mL. More than half of hydroxyzine positive drivers were female (57%) with a mean age of 42 years. Common drug combinations in this study involved antidepressants (74%), opioids (44%), and anticonvulsants (38%). Only seven cases have been reported involving a single substance, and four of these investigations have been presented. Behavioral observations included incoordination, slow and slurred speech, and difficulty following instructions on standardized field sobriety tests (SFSTs). Driving observations included erratic driving, crashes, driving in opposite lanes of travel, and running stop signs. This is concerning since hydroxyzine became the most identified antihistamine in this population in 2023 outpacing diphenhydramine.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005711","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":"Preparation and Stability Characterization of Flavor Ingredients in E-liquids for Pre-clinical Assessment of ENDS products: A case study of 38 flavor ingredients in a single mixture.","authors":"John H Miller, Thomas J Hurst, Niti Shah, Jingjie Zhang, F Frauendorfer, P Guy, P Diana, A Glabasnia, M Biasioli, J Hoeng, D Sciuscio, P Vanscheeuwijck, K Monica Lee","doi":"10.1093/jat/bkaf031","DOIUrl":"https://doi.org/10.1093/jat/bkaf031","url":null,"abstract":"<p><p>E-Vapor products generate aerosols typically containing nicotine, flavor ingredients, and aerosol formers (propylene glycol and vegetable glycerin). Whilst many flavor ingredients are \"generally recognized as safe (GRAS)\" for oral use in the food industry, there exist knowledge gaps on their effects when delivered by the inhalation route1,2. Due to the large number of available ingredients and potential combinations used to create e-liquids, toxicological and analytical evaluation of each flavor ingredient is impractical. Moreover, chemical characterization requires analytical methods to be developed and validated to measure key ingredients, as well as stability assessments to demonstrate that these test materials were stable during the testing period, which is equally challenging. In this study, we present a pragmatic approach of preparing \"pre-blends\" prior to making a test formulation, containing 38 flavor ingredients as an example case, ahead of pre-clinical toxicity testing. We used the pre-blends to simplify the preparation and the characterization of test formulations, establishing the stability criteria for the subsequent toxicity testing. We prepared pre-blends by dividing the 38 flavor ingredients into five (5) pre-blend groups based on structural moiety, solubility, and chemical reactivity. These pre-blends were mixed to make two different \"final\" test formulations (containing all 38 flavor ingredients with and without nicotine). We evaluated the stability of the pre-blends and the two test formulations prior to the subsequent in vivo inhalation studies. Based on the analytical assessment, all the pre-blends were stable up to 4 weeks at 0-4 ͦC. When all pre-blends were mixed, the test formulation was stable up to 3 days in the presence of nicotine and 10 days without nicotine when stored at 0-4 ͦC. These stability results were used to set the frequency of test formulations preparation for the in vivo inhalation studies, ensuring stability of test materials prior to the biological testing.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964716","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":"North America Laboratory Survey Data for Drug Testing in Drug Impaired Driving and Traffic Fatality Investigations.","authors":"Amanda L D'Orazio, Amanda L A Mohr, Ayako Chan-Hosokawa, Curt Harper, Marilyn A Huestis, Sarah Kerrigan, Jennifer F Limoges, Amy K Miles, Colleen E Scarneo, Karen S Scott, Barry K Logan","doi":"10.1093/jat/bkaf029","DOIUrl":"https://doi.org/10.1093/jat/bkaf029","url":null,"abstract":"<p><p>In 2004, the National Safety Council's Alcohol, Drugs and Impairment Division (NSC-ADID) set out to provide guidance for the standardization of laboratory testing practices in driving under the influence of drugs (DUID) and fatal motor vehicle crash investigations after identifying a lack of consistency in testing practices in this type of casework. A survey about laboratory testing practices, scopes of testing, and cutoffs was created using SurveyMonkey®, an online survey instrument, and sent to laboratories throughout the United States and Canada. Based on analysis of survey results and discussion, the first set of recommendations was published in 2007 with recommended scope and cutoffs for drug screening and confirmation in blood and urine. Subsequent surveys were sent to laboratories in 2012, 2016, and 2020, followed by updates to the recommendations published in 2013, 2017, and 2021. This publication highlights the 2024 survey results in addition to trends in drug testing practices and drug use positivity. With each survey year, data exhibited a shift of laboratories using newer and more sensitive technology such as Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) for screening and confirmation. Overall, data show that laboratories are willing to implement changes to be in compliance with the recommendations; however, challenges with instrument capacity and technology, lack of staffing, training, laboratory space constraints, and time associated with method development and validation hinder compliance with all of the recommendations. While compliance increased, 51% of laboratories reported using the practice of stop-limit testing, an administrative decision to stop testing if a blood alcohol concentration (BAC) result is at or above a certain concentration, which further hinders the understanding of the drug impaired driving problem. THC and/or metabolites remained the most prevalent drug reported by laboratories, followed by stimulants.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019578","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":"Validation of a novel LC-MS-MS method for the separation and differentiation of Δ8- and Δ9-tetrahydrocannabinol isomers and their major metabolites in antemortem whole blood.","authors":"Petronela Mikhaltsevich","doi":"10.1093/jat/bkaf003","DOIUrl":"10.1093/jat/bkaf003","url":null,"abstract":"<p><p>The 2018 Farm Bill legalized hemp and defined it as cannabis plant material having not more than 0.3% ∆9-tetrahydrocannabinol (∆9-THC) by dry weight. This has opened the door for the sale of hemp-derived ∆8-tetrahydrocannabinol (∆8-THC), a psychoactive isomer of ∆9-THC. Hemp has minimal amounts of naturally occurring ∆8-THC; however, the cannabidiol found in hemp can be chemically converted into ∆8-THC. Unfortunately, depending on the method of conversion, the amount of ∆8-THC, ∆9-THC, and other by-products can vary widely. For many laboratories, the emergence of ∆8-THC products resulted in analytical challenges because of the structural similarity of the isomers resulting in coelution. In response, a novel liquid chromatography-tandem mass spectrometry method was developed to separate the two isomers, with an improved limit of detection (LOD) and lower limit of quantification (LLOQ). With this method, clear separation was achieved between ∆9-THC and ∆8-THC and 11-nor-9-carboxy-∆9-tetrahydrocannabinol (∆9-THC-COOH) and 11-nor-9-carboxy-∆8-tetrahydrocannabinol (∆8-THC-COOH) and a partial separation of 11-hydroxy-∆9-tetrahydrocannabinol (∆9-THC-OH) and 11-hydroxy-∆8-tetrahydrocannabinol (∆8-THC-OH). While ∆9-THC-OH and ∆8-THC-OH did not achieve baseline separation, sufficient separation was achieved to confidently identify and differentiate the two compounds. LOD and LLOQ were the same for quantitative compounds. A quantitative range of 0.5-100 ng/mL was achieved for ∆9-THC, ∆8-THC, and ∆9-THC-OH and 2.5-250 ng/mL for ∆9-THC-COOH. Qualitative analysis with an LOD of 0.5 ng/mL was achieved for ∆8-THC-OH and 2.5 ng/mL for ∆8-THC-COOH. To achieve the desired LODs and LLOQs, alternate multiple reaction monitoring transitions were also explored in addition to those utilized in the laboratory's prior method and other published methods. The method was validated following the American National Standards Institute/Academy Standards Board Standard 036, Standard Practices for Method Validation in Forensic Toxicology with minor exceptions, and was proven to be reliable and robust.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"216-223"},"PeriodicalIF":2.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382417","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":"A validated method for capillary phosphatidylethanol 16:0/18:1 quantification with two different 10-µl volumetric absorptive microsample devices in the same setup.","authors":"Trine N Andreassen, Marina Gule, Hilde Havnen, Olav Spigset, Ragnhild Bergene Skråstad","doi":"10.1093/jat/bkaf004","DOIUrl":"10.1093/jat/bkaf004","url":null,"abstract":"<p><p>There is a growing interest for quantification of drugs in capillary blood. Phosphatidylethanol (PEth) is a biomarker for alcohol intake measured in whole blood, thus making it a candidate for capillary sampling. Our laboratory has been running a method for PEth quantification in venous blood since 2016, and we aimed to expand this method to also include capillary dried blood spot (DBS) samples. Two 10-µl volumetric absorptive microsampling (VAMS) devices, Capitainer®B Vanadate and Mitra®, were included in the method development and validated. Calibrators and quality controls were spiked during automatic sample extraction without the VAMS devices present, making it possible to extract and analyze both types of VAMS samples in the same setup. With the Mitra device, all pre-established validation criteria were fulfilled in the measuring range of 0.03 to 4.0 µM (21-2812 ng/mL), including method comparison with our venous blood method. Capitainer fulfilled all validation criteria, except for the accuracy of samples with PEth levels ≥ 0.5 µM (≥ 352 ng/mL) (deviation -17.1% to -20.5%). The correlation analysis between Capitainer and the venous blood results showed no constant bias, but an acceptable small proportional mean difference of -7.6%. Overall, the method validation results for both Capitainer and Mitra were considered acceptable. Both devices were found to be suitable for the analyses of PEth.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"231-240"},"PeriodicalIF":2.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065800","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":"Determination of tramadol and its metabolite O-desmethyltramadol in vitreous humor. Is it helpful in forensic casework?","authors":"Kalliopi Vasileiou, Panagiota Nikolaou, Artemisia Dona, Stavroula Papadodima, Sotirios Athanaselis, Chara Spiliopoulou, Ioannis Papoutsis","doi":"10.1093/jat/bkae088","DOIUrl":"10.1093/jat/bkae088","url":null,"abstract":"<p><p>In recent years, there has been increasing interest on the use of alternative biological materials in forensic toxicology. Vitreous humor is one of them, which, due to the closed cavity it is contained, has a low degree of contamination and high purity that makes it ideal for use in postmortem specimens. The aim of this study was to investigate the distribution of tramadol and its active metabolite O-desmethyltramadol in vitreous humor and the usefulness of using this alternative biological matrix in tramadol-related forensic cases. For this purpose, a gas chromatography-mass spectrometric method for the determination of the two analytes in blood and vitreous humor samples, which included solid-phase extraction and derivatization using N,O-Bis(trimethylsilyl)trifluoroacetamide with 1% trimethylsilyl chloride, was developed. The method was fully validated according to international guidelines and was applied to blood and vitreous humor samples from 12 forensic cases. Both substances were found to be readily distributed in vitreous humor, since even in cases of very low concentrations of the analytes in blood, their detection was also possible in vitreous humor. In addition, the vitreous humor to blood concentration ratios were calculated for both substances and the mean values were found to be 0.91 for tramadol and 0.94 for O-desmethyltramadol. The results of our study indicate that the information that can be extracted from the analysis of vitreous humor samples is particularly useful during the investigation of tramadol-related cases. Nevertheless, the need for further study of this alternative material to establish therapeutic and toxic limits becomes apparent.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"280-288"},"PeriodicalIF":2.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414388","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}

{"title":"Identification of in vivo and in vitro metabolites of fentanyl using UHPLC-Q-Orbitrap-HRMS.","authors":"Meng Liu, Sen Zhao, Bin-Jie Wang, Hong Zhou, Yao Liu","doi":"10.1093/jat/bkaf012","DOIUrl":"10.1093/jat/bkaf012","url":null,"abstract":"<p><p>A comparative analysis of the metabolites and metabolic pathways of fentanyl was conducted in liver microsomes and zebrafish models utilizing ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). A total of 21 metabolites were identified across both liver microsomes and zebrafish models. These included 9 Phase I metabolites, such as N-dealkylated, N-oxidated, and hydroxylated products, and 12 Phase II metabolites, including glucuronidated, methylated, and sulfated products, as well as a series of products derived from conjugation with glutathione (GSH). Notably, the products derived from conjugation with GSH are reported here for the first time. This study provides a comprehensive and in-depth comparative analysis of fentanyl metabolism in liver microsomes and zebrafish, offering a foundation for analyzing and identifying biological samples in cases of fentanyl misuse and fatalities.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"248-257"},"PeriodicalIF":2.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425357","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 (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol and (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabinol in hair from a school-age population.","authors":"Ryan B Paulsen, G Neil Stowe, Michael I Schaffer, Nickolaus Krohn","doi":"10.1093/jat/bkaf020","DOIUrl":"10.1093/jat/bkaf020","url":null,"abstract":"<p><p>A sensitive liquid chromatography-tandem mass spectrometry method for the detection of (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol and (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabinol in hair with a cutoff of 1 pg/10 mg of hair and a limit of quantitation of 0.2 pg/10 mg of hair for both analytes was developed and is herein described. A subset of samples collected from a school-age population between December 2022 and February 2023 was analyzed using this method after having screened presumptive positive by enzyme immunoassay out of a total pool of approximately 5300 samples. Of these presumptive positive samples, 66% showed the presence of one or both analytes at a concentration ≥1 pg/10 mg of hair. Of the 213 positive samples, 57% contained more (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabinol than (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol and 6% contained more than 50-fold higher Δ8 isomer than Δ9 isomer. Of the 197 samples that were reportable for (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol ≥1 pg/10 mg cutoff, 53% of them contained more (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabinol than (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol. Of the 197 samples that were reportable for (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabinol ≥1 pg/10 mg cutoff, 15.7% exceeded the upper limit of linearity of the method (200 pg/10 mg). These results suggest a high level of (-)-Δ8-tetrahydrocannabinol usage in this population relative to (-)-Δ9-tetrahydrocannabinol usage. They further suggest the possibility that (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol reported for some of these samples may only have been present due to (-)-Δ9-tetrahydrocannabinol contamination of (-)-Δ8-tetrahydrocannabinol products being consumed in large quantities. Thus, reported results for (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol alone may give a false picture of the extent of the cannabis product being consumed by a test subject.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"224-230"},"PeriodicalIF":2.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556956","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":"Blood to serum concentration ratios for ethyl glucuronide and ethyl sulfate after five drinking episodes.","authors":"Matthias Bantle, Annette Thierauf-Emberger, Alexandra Schröck, Wolfgang Weinmann, Lorenz M Bell","doi":"10.1093/jat/bkaf006","DOIUrl":"10.1093/jat/bkaf006","url":null,"abstract":"<p><p>Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are mostly analyzed in urine; consequently, most kinetic studies are based on urine samples. In forensic cases, however, it may be necessary to determine these alcohol biomarkers in serum, whole blood, or capillary blood. While there are sufficient data on EtG and EtS in serum after alcohol consumption, the amount of data available on whole blood concentrations is small. Therefore, data on corresponding blood-to-serum ratios seem to gain importance. This study provides data on a drinking experiment with 5 drinking episodes, where serum and whole blood samples were taken simultaneously from 11 healthy participants over 10 days. The samples were analyzed for EtG, EtS, and ethanol. EtG and EtS analysis in whole blood and serum were performed by liquid chromatography-tandem mass spectrometry; ethanol was determined by gas chromatography-flame ionization detection and an alcohol dehydrogenase-based method. EtG and EtS reached their maximum concentration 4-7 h after alcohol consumption. For EtG, a mean blood-to-serum ratio of 0.58 with a range from 0.38 to 0.73 was found; for EtS, the mean ratio was 0.81 with a range from 0.61 to 0.92, indicating a predominant distribution in the serum. For both analytes, high correlation coefficients were obtained when plotting concentrations in serum against concentrations in whole blood. Concerning elimination profiles of the individuals, no time or concentration dependence of EtG or EtS blood-to-serum ratios could be deduced. Neither for EtG nor for EtS was a regularity of curve progressions observed in our test specimens.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"241-247"},"PeriodicalIF":2.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408005","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":"Pregabalin concentrations: establishing 'normal' and 'cause for concern' concentration ranges in postmortem blood.","authors":"Limon Khatun Nahar, Sue Paterson","doi":"10.1093/jat/bkaf005","DOIUrl":"10.1093/jat/bkaf005","url":null,"abstract":"<p><p>Pregabalin (PGL) is prescribed for the treatment of neuropathic pain, epilepsy, and general anxiety disorder; however, studies have shown that PGL is being misused. It is generally accepted that those who misuse PGL use it in amounts significantly greater than the recommended therapeutic dose. In some instances, such high doses may be well tolerated, and in some instances, the same dose may cause death. Individual variation and postmortem (PM) changes make it extremely challenging for toxicologists to determine if a drug concentration found at PM was contributory to death or not. Unfortunately, meaningful PM data, which can help with interpreting PGL concentrations in femoral-vein blood, are rare. Only one recommendation was found where an author suggested that a PGL concentration of >25 µg/mL in PM blood should be considered as significant; however, in this case series PGL was only screened for in specific cases. To aid interpretation of PGL concentrations, reference data from toxicological analysis conducted on femoral-vein blood only from all manners of death are needed to compile meaningful and unbiased concentration ranges. This study looked at PGL femoral-vein blood concentrations in PM cases from all manners of death over a 2-year period. As it is impossible to define a PM concentration that should be considered toxic/fatal, this study aimed to provide a concentration cut-off where the PGL may be considered a 'normal' incidental finding (unlikely to be the cause of death) or a 'cause for concern' where it may have been taken in excess and caused or contributed to death. This study recommends that a PGL concentration of ≥20 µg/mL in femoral-vein blood should be considered as significant and a 'cause for concern'. Concentrations of ≤19 µg/mL may be considered a 'normal' incidental finding in death, but tolerance and other drug findings need to be considered.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"272-279"},"PeriodicalIF":2.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122843","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}