Journal of analytical toxicology最新文献

{"title":"Method for detection of naturally occurring toxins in human urine using liquid chromatography-high-resolution mass spectrometry.","authors":"Bryan E Hettick, Anisha Saddy, Logan C Krajewski, Rudolph C Johnson, Elizabeth I Hamelin","doi":"10.1093/jat/bkae086","DOIUrl":"10.1093/jat/bkae086","url":null,"abstract":"<p><p>Natural toxins present an ongoing risk for human exposure that requires a rapid and accurate diagnosis for proper response. In this study, a qualitative liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method was developed and validated for the detection of a large, diverse selection of natural toxins. Data-dependent acquisition was performed to identify compounds with an in-house mass spectral library of 129 hazardous toxins that originate from plants, animals, and fungi. All 129 compounds were spiked into human urine, extracted, and evaluated for spectral library matching. Of these, 92 toxins met the quality criteria and underwent validation in urine matrix based on American National Standards Institute guidelines. A generalized workflow for method expansion was developed and enables the rapid addition of relevant compounds to the established method. This LC-HRMS method achieves efficient detection of natural toxins in urine, and the created workflow can rapidly increase compound coverage via method expansion.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"36-42"},"PeriodicalIF":2.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557786","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 an LC-MS-MS method for analysis of 58 drugs of abuse in oral fluid and method comparison with an established LC-HRMS method.","authors":"Yufang Zheng, Magnus A B Axelsson, Moa Andresen Bergström","doi":"10.1093/jat/bkae087","DOIUrl":"10.1093/jat/bkae087","url":null,"abstract":"<p><p>Liquid chromatography-mass spectrometry (LC-MS) methods for detection of multiple drugs of abuse (DoA) in oral fluid (OF) samples are being implemented in many clinical routine laboratories. Therefore, there is a need to develop new multianalyte methods with simple sample pretreatment and short analysis times. The purpose of this work was to validate a method detecting 58 DoA to be used with two different OF sampling kits, the saliva collection system (SCS) from Greiner Bio-One and Quantisal from Immunalysis, using the same sample pretreatment and analytical method. A set of 110 samples collected with the SCS kit was further compared to an high-resolution mass spectrometry (LC-HRMS) method in another laboratory. The method was successfully validated, with precision and accuracy of ≤15% and z-scores of <2 for external controls. Using a sensitive LC-MS-MS instrument, the detection limits were <1 µg/l in neat oral fluid. In the comparative study between the LC-MS-MS and LC-HRMS methods using SCS samples, a good agreement was observed. Discrepancies were limited to lower concentration ranges, attributable to differences in cut-off thresholds between the methods. This work contributes to the development of LC-MS multianalyte methods for OF samples, which are suitable for clinical routine laboratories.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"14-25"},"PeriodicalIF":2.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567128","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":"Liquid-liquid extraction solvent selection for comparing illegal drugs in whole blood and dried blood spot with LC-MS-MS.","authors":"Melike Aydoğdu, Hasan Ertaş, Fatma Nil Ertaş, Serap Annette Akgür","doi":"10.1093/jat/bkae081","DOIUrl":"10.1093/jat/bkae081","url":null,"abstract":"<p><p>This study focused on the simultaneous detection of amphetamine, 3,4-methylenedioxy methamphetamine, morphine, benzoylecgonine, and 11-nor-9-carboxy-tetrahydrocannabinol in whole blood and dried blood spot (DBS). It is aimed to select a solvent mixture for liquid-liquid extraction technique employing liquid chromatography-tandem mass spectrometry (LC-MS-MS). The obtained DBS results were compared with the whole blood samples results. A simple, rapid, and reliable LC-MS-MS method was developed and validated for all analytes in whole blood and DBS. LC was performed on a Hypersil Gold C18 column with an initial gradient of 0.01% formic acid, 5 mM ammonium format buffer in water, and acetonitrile at 0.3 ml/min with 7.5 min runtime. A methanol:acetonitrile (40:60 v/v) mixture was selected for both matrices. Limit of quantitation (LOQ) values were 10-25 ng/mL; linear ranges were LOQ-500 ng/ml for all analytes; correlation coefficients were greater than 0.99, and all calibrator concentrations were within 20%. Analytical recovery in blood and DBS ranged from 84.9% to 113.2% of the expected concentration for both intra- and inter-day. Analytes were stable for 1, 10, and 30 days after three freeze/thaw cycles. It was determined that the variances of the results obtained with the two matrices in the comparison study were equal for each analyte, and the results were highly correlated (r = 0.9625). A sensitive, accurate, and reliable chromatographic method was developed to determine amphetamine, 3,4-methylenedioxy methamphetamine, morphine, benzoylecgonine, and cannabis, by performing the same preliminary steps with whole blood and dried blood spots. It was observed that the results obtained in these two matrices were compatible and interchangeable when statistically compared.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"26-35"},"PeriodicalIF":2.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375418","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":"Long-term stability of sufentanil quantified by UPLC-MS-MS in human plasma frozen for 11 years at -20°C.","authors":"Andreas Wehrfritz, Stefanie Schmidt, Harald Ihmsen, Jürgen Schüttler, Christian Jeleazcov","doi":"10.1093/jat/bkae083","DOIUrl":"10.1093/jat/bkae083","url":null,"abstract":"<p><p>The long-term stability of drug concentrations in human plasma samples, when stored under normal laboratory conditions over several years, is important for research purposes and clinical re-evaluation, and forensic toxicology. Fifty human plasma samples from a former clinical trial were re-analyzed after storage at -20°C for 11 years. Plasma samples were extracted using solid-phase extraction. Isotope labeled sufentanil-d5 was used as internal standard. Sufentanil plasma concentrations were determined by ultra-performance liquid chromatography with gradient elution, followed by tandem mass spectrometry with electrospray ionization. The linear dynamic range was 25-2500 pg/mL, the limit of detection was 10 pg/mL, and the lower limit of quantification was 25 pg/mL. Intra- and inter-assay error did not exceed 6%. The deviation of the measured sufentanil plasma concentrations between the re-analysis and the first analysis was -63 ± 14% (mean ± SD). Therefore, sufentanil concentrations in human plasma were not stable in samples frozen at -20°C over 11 years.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"59-62"},"PeriodicalIF":2.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465977","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":"Ethanol stability from 9 years of a blind quality control program in blood alcohol analysis.","authors":"Erika Phung, Corissa Rodgers, Andrea Gooden, Peter Stout, Dayong Lee","doi":"10.1093/jat/bkae085","DOIUrl":"10.1093/jat/bkae085","url":null,"abstract":"<p><p>A blind quality control (BQC) program in blood alcohol analysis was implemented at the Houston Forensic Science Center (HFSC) in September 2015. By mimicking authentic toxicology blood evidence, the laboratory can perform a concurrent evaluation of their technical and administrative casework procedures and test the accuracy and reliability of their volatile analysis method in a format that is blinded to the analyst. From September 2015 to November 2023, HFSC's Quality Division submitted 1228 antemortem whole-blood samples: 292 ethanol-negative samples and 936 ethanol-positive samples at 16 target concentrations (0.051, 0.080, 0.100, 0.110, 0.120, 0.130, 0.150, 0.160, 0.170, 0.180, 0.190, 0.200, 0.230, 0.240, 0.250, and 0.260 g/dL). A second, unopened blood tube in 168 of the 1228 BQCs was also analyzed after 721-1140 days: 24 ethanol-negative samples and 144 ethanol-positive samples at 5 target concentrations (0.080, 0.100, 0.130, 0.180, and 0.240 g/dL). All 316 ethanol-negative samples remained negative. After 42-758 days, the average (median, range) change in ethanol concentration of the 936 positive samples was -1.4% (-1.3%, -12.0% to +8.4%) with a statistically significant difference (P < .001) observed for the gradual decline in blood alcohol concentration (BAC) over time. The average BAC percentage differences per target concentration, ranged from -6.4% (-0.008 g/dL) to +5.7% (+0.011 g/dL), were within HFSC's current measurement uncertainty (9.4% at k = 3), showing no apparent correlation between the change in ethanol and the theoretical target concentration. As the analysis time between the two blood specimens from the same evidence kit extended, the loss in ethanol significantly increased (P < .001).</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"53-58"},"PeriodicalIF":2.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557787","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":"Comprehensive evaluation of cocaine and its hydroxy metabolites in seized cocaine and a large cohort of hair samples.","authors":"Milena M Madry, Teresa Denifle, Tina M Binz, Christian Bogdal, Thomas Kraemer, Markus R Baumgartner","doi":"10.1093/jat/bkae064","DOIUrl":"10.1093/jat/bkae064","url":null,"abstract":"<p><p>As cocaine (COC) is not only incorporated into hair via blood following ingestion but also by external contamination, hair samples are commonly tested for COC metabolites to prove ingestion. However, COC metabolites can also be present as degradation products in typical street COC samples. The present study investigates minor hydroxycocaine (OH-COC) metabolites p- and m-OH-COC together with p- and m-hydroxybenzoylecgonine (OH-BE) in seized COC (n = 200) and hair samples from routine case work (n = 2389). Analytical results of hair samples were interpreted using an established decision model for the differentiation between actual use and external contamination using metabolic ratios (metabolite to COC). They were further examined concerning background of request, hair color, body site of sample collection, sex, and metabolic ratios of the main metabolites [benzoylecgonine (BE), norcocaine (NC), and cocaethylene (CE)]. All seized COC samples were positive for p- and m-OH-COC with a maximum percentage of 0.025% and 0.052%, respectively; p- and m-OH-BE were detected in 55% and 56% of samples with a maximum percentage of 0.044% and 0.024%, respectively. Analytical results of 424 hair samples (17.7%) were interpreted as being predominantly from contamination; the majority of these samples were from traffic medicine cases (83.7%). Metabolic ratios of minor OH-COC metabolites were significantly higher in hair samples interpreted as originating from use than in samples interpreted as caused by contamination. Metabolic ratios for OH-COCs were significantly higher in forensic cases compared to abstinence controls and also in black hair compared to blond/gray hair. However, this was not the case for OH-BE metabolic ratios. No statistical difference was observed with regard to the donor's sex. OH-COC metabolic ratios increased significantly with increasing ratios of NC and CE to COC, respectively. The study demonstrates that OH-COC metabolites (including thresholds for their metabolic ratios) must be used for a reliable interpretation of positive COC results in hair samples.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"672-683"},"PeriodicalIF":4.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035940","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":"Assessment of postmortem urine fentanyl detection by autopsy dipstick testing in accidental overdose deaths.","authors":"Anson Tsang, Luke N Rodda","doi":"10.1093/jat/bkae072","DOIUrl":"10.1093/jat/bkae072","url":null,"abstract":"<p><p>Accidental overdose cases continue to rise due to the opioid epidemic in the USA, namely, the widespread availability and use of fentanyl. Medical examiners and coroners across the country have been subsequently burdened, and with limited resources, some seek alternative triaging processes to identify overdoses. Point-of-care urine dipstick testing at autopsy is one such idea that may be used in various ways to instigate or negate the need for an autopsy or regular forensic toxicology laboratory testing. This study investigated the frequency and estimated quantitative fentanyl and norfentanyl concentrations in the postmortem urine of fentanyl-related accidental overdose deaths, as well as the effectiveness of commercially available point-of-care urine dipstick tests based on such concentrations. A total of 1550 fentanyl-related accidental overdose cases, where both the postmortem peripheral femoral blood and urine were tested, were reviewed. Of these, using sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) laboratory testing, 82 cases (5%) had a positive fentanyl or norfentanyl detection in the blood, while fentanyl or norfentanyl remained undetected in the urine. Furthermore, a comparison of commercially available urine dipstick test cut-offs and authentic casework with estimated urine concentrations revealed that at a fentanyl/norfentanyl cut-off level of 5 ng/mL, 19% of these fentanyl-related accidental overdoses would result in a false negative, 24% at 10 ng/mL, 25% at 20 ng/mL, 51% at 50 ng/mL, and 61% at 100 ng/mL. The study found that the use of urine dipstick tests, as a decision-maker for the initiation of further comprehensive routine toxicology laboratory testing, or to support cause and manner of death determination, leads to both false-positive and false-negative predictions in fentanyl accidental overdoses.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"667-671"},"PeriodicalIF":4.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132801","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":"Identification of 5-aminometonitazene and 5-acetamidometonitazene in a postmortem case: are nitro-nitazenes unstable?","authors":"Claire Parks, Peter D Maskell, Denise A McKeown, Lewis Couchman","doi":"10.1093/jat/bkae076","DOIUrl":"10.1093/jat/bkae076","url":null,"abstract":"<p><p>In recent years, the use of 2-benzylbenzimidazole opioids ('nitazenes') has increased with them becoming one of the most prominent synthetic opioid subclasses of novel psychoactive substances. With the increased prevalence, there is also a concern of the dangers to public health with the use of nitazenes due to their high potency especially with polypharmacy. To aid in the detection of such compounds, it is important that forensic toxicology laboratories maintain up-to-date compound libraries for drug screening methods and that sensitive analytical instrumentation is available to detect the low blood/plasma concentrations of more potent drugs. This includes not only the compounds themselves but also potential metabolites and/or degradation products. Metonitazene is a 'nitro-nitazene' with a nitro group at position 5 of the benzimidazole ring. As a nitro-nitazene, there is a potential for bacterial degradation of metonitazene to 5-aminometonitazene, as occurs with nitro-benzodiazepines. In this study, we provide evidence from a postmortem (PM) case of degradation of metonitazene in unpreserved PM blood using liquid chromatography-triple quadrupole mass spectrometry (LC-QQQ-MS), and putative identification of the degradation/metabolic products 5-aminometonitazene and 5-acetamidometonitazene by liquid chromatography-quadrupole time-of-flight mass spectrometry. The results from LC-QQQ-MS analysis indicated that there did not appear to be such degradation in preserved (fluoride/oxalate) blood. These results suggest that nitro-nitazenes may be subject to similar in vitro stability/degradation issues as nitro-benzodiazepines. These breakdown products should be added to instrument libraries to aid in the detection of the use of nitro-nitazenes, and nitro-nitazenes should be quantified in preserved blood samples where available.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"691-700"},"PeriodicalIF":2.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107659","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":"Detection of \"smoke powder\" etomidate and its metabolite etomidate acid in blood and urine by UHPLC-MS-MS: application in authentic cases.","authors":"Zhou Liying, Zhao Junbo, Xie Wanting, Xiang Ping, Shi Yan, Wu Hejian, Yan Hui","doi":"10.1093/jat/bkae080","DOIUrl":"10.1093/jat/bkae080","url":null,"abstract":"<p><p>Recently, etomidate has been widely used as an alternative in illicit drug market. It is usually added to regular cigarette tobacco (commonly known as \"cigarette powder\") or mixed in e-cigarette oil sold through the Internet, retail stores, or entertainment outlets and other channels. An ultra-high performance liquid chromatography tandem mass spectrometry method was developed to quantify etomidate and etomidate acid in human blood and urine. The limit of detection (LOD) of etomidate and etomidate acid in blood is 0.5  and 2 ng/mL, respectively, and the lower limit of quantification (LLOQ) is 1  and 5 ng/mL, respectively. The LOD of etomidate and etomidate acid in urine is 1 and 2 ng/mL, respectively, and the LLOQ is 2  and 5 ng/mL, respectively. The precision, accuracy, recoveries, and matrix effects of etomidate and etomidate acid determinations in blood and urine met the requirements for methodological validation. The method was successfully applied to the identification and quantification of etomidate and etomidate acid in blood and urine of 62 forensic cases. The concentration of etomidate ranged from 1.52 to 8.41 ng/mL (positive cases, n = 5) and the concentration of etomidate acid ranged from 2.76 to 112 ng/mL (positive cases, n = 5) in blood. The concentrations of etomidate and etomidate acid in urine samples were 2.64-79,300 ng/mL (positive cases, n = 59) and 6.11-518,000 ng/mL (positive cases, n = 60), respectively. Therefore, the concentration of etomidate in blood and urine is mostly higher than that of etomidate.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"701-709"},"PeriodicalIF":4.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347102","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":"Deaths involving novel benzodiazepines in Victoria, Australia from 2018 to 2022.","authors":"Olaf H Drummer, Samantha Joubert, Matthew Di Rago, Jared W Castle, Kerryn Crump, Linda Glowacki, Dimitri Gerostamoulos","doi":"10.1093/jat/bkae075","DOIUrl":"10.1093/jat/bkae075","url":null,"abstract":"<p><p>Novel benzodiazepine (NBz) detections in Victorian coronial cases started early in 2018 and have continued to increase in number and type up to December 2022. The 11 different NBz detections included etizolam (n = 82), flualprazolam (n = 43), clonazolam or 8-aminoclonazolam (n = 30), bromazolam (n = 15), clobromazolam (n = 13), phenazepam (n = 13), flubromazolam (n = 12), flubromazepam (n = 8), desalkylflurazepam (n = 6), diclazepam (n = 2), and estazolam (n = 1). The pattern of detections varied over the 5-year period, with different compounds appearing over different time frames. The most recent NBz to appear were bromazolam, clobromazolam, flubromazepam, and phenazepam, whereas etizolam had been seen regularly in case work since 2018. Of the total 133 deaths, 95 were considered drug-related deaths by forensic pathologists with at least one additional CNS depressant also present capable of contributing to death. All deaths involved other (non-benzodiazepine) CNS active drugs, although many involved multiple NBz, with five or more different benzodiazepines detected in eight cases.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"684-690"},"PeriodicalIF":4.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080384","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}