Journal of analytical toxicology最新文献

{"title":"Protonitazene metabolite variability in post-mortem casework.","authors":"Rebecca Wood, Robert Moore","doi":"10.1093/jat/bkaf042","DOIUrl":"https://doi.org/10.1093/jat/bkaf042","url":null,"abstract":"<p><p>Protonitazene is a highly potent synthetic opioid that has recently emerged in the illicit drug supply. Data on its metabolism and the detection of its metabolites in post-mortem specimens are limited. This study retrospectively analysed 14 post-mortem cases to investigate metabolite profiles in blood and urine using high-resolution mass spectrometry. Detected metabolites included 5-aminoprotonitazene, N-desethylprotonitazene, and 4-hydroxynitazene. Additionally, a novel metabolite, hydroxyprotonitazene, previously only observed in liver microsome models, was identified. Significant variability in the metabolites detected across cases was observed, likely influenced by differences in metabolism, post-mortem changes, sampling methods, and metabolite stability. This study underscores the challenges of detecting protonitazene exposure and highlights the necessity of targeting multiple metabolites, as no single marker reliably indicated protonitazene use. Further research is needed to confirm metabolite identities, evaluate their stability, and understand their role in protonitazene toxicity.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020767","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":"Drug transfer during intimate moments can produce an adverse analytical finding during a doping control. Case report with ligandrol.","authors":"Pascal Kintz, Laurie Gheddar","doi":"10.1093/jat/bkaf041","DOIUrl":"https://doi.org/10.1093/jat/bkaf041","url":null,"abstract":"<p><p>Selective androgen receptor modulators (SARMs) are a new class of substances that have similar properties to anabolic steroid agents, but with marked reduced androgenic properties. As SARMs have the potential to be misused for performance enhancement in sport due to their anabolic properties as well as ability to stimulate androgen receptors in the muscle and the bone, they have been prohibited at-all-times by the World Anti-Doping Agency (WADA) since 2008 under section S1.2 of the List. Ligandrol is one of the more popular SARMs. A WADA accredited laboratory identified in the urine of a female athlete bishydroxy-ligandrol, the major ligandrol metabolite at approx. 90 pg/mL (specimen A) and 200 pg/mL (specimen B). The athlete challenged this anti-doping rule violation and requested a hair test to document possible incidental exposure. About 7 weeks after urine collection, a hair specimen (brown in color and > 20 cm in length) was collected and segmented in 6 x 1 cm segments. Ligandrol was tested by liquid chromatography-tandem mass spectrometry after alkaline incubation and extraction. With a limit of quantitation at 1 pg/mg, no ligandrol was identified. It appears that the athlete was unaware her husband was taking the substance, which was confirmed by his hair test (ligandrol at 7 and 8 pg/mg in 2 x 2.5 cm segments). The Court of Arbitration for Sports accepted the athlete's explanation that she had been exposed to ligandrol through the exchange of bodily fluids with her husband and lifted her provisional ban. This case demonstrates that drug transfer between two subjects is possible during intimate moments.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001660","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":"Medetomidine Quantitation and Enantiomer Differentiation in Biological Specimens Collected After Fatal and Non-Fatal Opioid Overdoses.","authors":"Sara E Walton, Brianna N Stang, Sherri Kacinko, Donna M Papsun, Barry K Logan, Alex J Krotulski","doi":"10.1093/jat/bkaf040","DOIUrl":"https://doi.org/10.1093/jat/bkaf040","url":null,"abstract":"<p><p>Medetomidine is an alpha-2 agonist and non-opioid sedative. Its presence in illicit fentanyl and heroin drug supplies poses significant risks to user health caused by cardiac effects and sedation. Medetomidine exists in two enantiomeric forms: dexmedetomidine and levomedetomidine. Dexmedetomidine is used in humans in medical settings, while dexmedetomidine alone and a racemic mixture of dexmedetomidine and levomedetomidine are used in animals in veterinary settings. Little information is known about circulating blood concentrations of medetomidine or its enantiomers in humans in situations involving synthetic opioids (e.g., fentanyl) and other sedatives (e.g., xylazine, benzodiazepines). A new toxicological workflow using liquid chromatography tandem quadrupole mass spectrometry (LC-QQQ-MS) was developed and validated for the quantitation of medetomidine and the qualitative enantiomeric separation of dexmedetomidine and levomedetomidine. The assays were applied to a case series of 100 authentic specimens from emergency department admissions and forensic postmortem investigations containing medetomidine, fentanyl, xylazine, and metabolites, among other substances. Medetomidine blood concentrations in non-fatal overdoses ranged 0.1-16 ng/mL (median: 1.5 ng/mL) and in fatal overdoses ranged 0.1-32 ng/mL (median: 0.31 ng/mL). Xylazine was co-detected in 76% of cases with higher median concentrations: 8.3 ng/mL (non-fatal) and 15 ng/mL (fatal). Fentanyl was co-detected in 93% of cases with median concentrations of 5.2 ng/mL (non-fatal) and 21 ng/mL (fatal). Dexmedetomidine and levomedetomidine were identified in 90% of cases; the remaining cases were confirmed or suspected medical-setting administration of dexmedetomidine. These findings demonstrate that medetomidine is arising from veterinary or clandestine sources, and we hypothesize the latter. Recreational medetomidine use causes adverse effects such as profound bradycardia and heightened sedation, especially when combined with fentanyl and xylazine. Forensic laboratories must remain aware of adulterants, like medetomidine, appearing in traditional opioid products (e.g., fentanyl, heroin), updating testing methods to capture these emerging adulterants in real-time.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967815","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 production in the gut: An autopsy case.","authors":"Maiko Kusano, Chikara Kohda, Masaya Fujishiro, Taka-Aki Matsuyama","doi":"10.1093/jat/bkaf039","DOIUrl":"https://doi.org/10.1093/jat/bkaf039","url":null,"abstract":"<p><p>Postmortem alcohol production by microorganisms has been known to increase blood alcohol concentration, potentially leading to erroneous interpretation. Here, we present a peculiar case where postmortem toxicology detected a high ethanol concentration only in the stomach content. An 87-year-old bedridden female was taken to senior day care facility, where the nurse attempted to take her vitals but noticed she was not breathing. The facility called for an ambulance but she was pronounced dead soon after arriving at the hospital. She was found to be severely dehydrated and her blood tests indicated poor health. Autopsy was performed two days after death, and postmortem alcohol analysis detected a high ethanol concentration only in the stomach content. Our aim was to investigate the causative agent of ethanol production; microbiological analysis identified the yeast species Candida glabrata as the responsible microorganism.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984712","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 Screening and Confirmation Method for 946 Drugs and Metabolites Using LC-QTOF-MS with SWATH Acquisition.","authors":"Maria Sarkisian, Luke N Rodda","doi":"10.1093/jat/bkaf037","DOIUrl":"https://doi.org/10.1093/jat/bkaf037","url":null,"abstract":"<p><p>A streamlined liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) method utilizing protein precipitation and filtration extraction was developed to achieve rapid and reliable screening and confirmation for blood and urine matrices. This method targets 946 drugs and metabolites across 35 drug classes via sequential window acquisition of all theoretical mass spectra (SWATH) acquisition with variable customized windows to enhance spectral clarity, and was validated per established guidelines to ensure high accuracy and reproducibility. Combined with complementary in-house methods, this approach meets and exceeds the testing requirements outlined in ANSI/ASB standards and recommendations for postmortem, drug-facilitated crime (DFC) and Tier I and II driving under the influence of drug (DUID) analyses. The method demonstrated efficient and sensitive performance, achieving limits of detection as low as 0.1 ng/mL. It accurately identified expected detections across 67 proficiency test samples and 224 authentic case samples, with high accuracy and reliability in the detection of both traditional drugs and novel psychoactive substances (NPS). The method employs an in-house built library and incorporates in-batch standards analyzed alongside case samples to ensure contemporaneous identification criteria, making it suitable for confirmation and reporting purposes. By expanding the analytical capabilities to include a vast range of analytes, this method improves the likelihood of identifying substances that may otherwise go undetected, and reduces the need for multiple separate tests, thereby enhancing the overall effectiveness of toxicological investigations.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964574","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":"From Promise to Practice: Why HRMS Has Yet to Fully Revolutionize Forensic Toxicology.","authors":"Luke N Rodda, Kayla N Ellefsen, Marie Mardal, Peter Stockham, Andrea E Steuer, Dani Mata, Alex J Krotulski, Maria Sarkisian","doi":"10.1093/jat/bkaf036","DOIUrl":"https://doi.org/10.1093/jat/bkaf036","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019062","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":"Lateral flow immunoassay for amatoxins detection in human urine compared to liquid chromatography-high-resolution tandem mass spectrometry.","authors":"Aline C Vollmer, Thomas P Bambauer, Candace B Bever, Christina C Tam, Lea Wagmann, Markus R Meyer","doi":"10.1093/jat/bkaf018","DOIUrl":"https://doi.org/10.1093/jat/bkaf018","url":null,"abstract":"<p><p>Amatoxin-containing mushrooms, which contribute to many intoxications each year are of particular interest for clinicians and toxicologists as patients require special treatment in hospital. To confirm the presence of amatoxins, approaches for their fast, sensitive, and reliable identification must be available. Solid-phase extraction followed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) is widely applied for analysis of amatoxins as this combination provides suitable sensitivity, specificity, and mass accuracy. Nevertheless, time-consuming preparatory steps as well as expensive equipment is required. Therefore, a lateral flow immunoassay (LFIA) for trace detection of α-, β-, and γ-amanitin was established and evaluated using dog urine. In this study, we answered the questions whether this LFIA can be transferred to human urine samples, and whether this LFIA can be used as a supporting tool prior to LC-HRMS/MS confirmation. Result interpretation by eye and using digitally-acquired pixel intensity ratios was investigated with respect to analytical sensitivity. The LFIA detects amatoxins in human urine after visual evaluation to as little as 5 ng/mL (α-amanitin - 10 ng/mL, β-amanitin - 50 ng/mL, γ-amanitin - 5 ng/mL). After digital analysis, pixel intensity ratios were determined to evaluate the LFIA as positive, negative, or trace result. Detection limits were redefined ranging from 1 ng/mL (α- and γ-amanitin) to 3 ng/mL (β-amanitin). For the proof-of-concept, 73 human urine samples submitted to the authors´ laboratory for toxicological analysis were analyzed using the LFIA and LC-HRMS/MS. Only three out of 73 urine samples were tested false positive with the LFIA as LC-HRMS/MS confirmation revealed no detection of amatoxins. Sixteen urine samples were evaluated as trace results and confirmed negative using LC-HRMS/MS except for one case which was positive for α-amanitin but negative for β-amanitin. Although particularly positive and trace results of the LFIA still need to be confirmed, the negative LFIA results correlated well with LC-HRMS/MS.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990838","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":"How diquat kills: Investigation of the toxicological profiles of diquat and bromide ion concentrations in serum by LC-MS/MS and capillary electrophoresis in a suicide case.","authors":"Maiko Kusano, Yoshiaki Iwamuro, Takero Terayama, Takaya Murakami, Masaya Fujishiro, Taka-Aki Matsuyama","doi":"10.1093/jat/bkaf035","DOIUrl":"https://doi.org/10.1093/jat/bkaf035","url":null,"abstract":"<p><p>Herbicide poisoning commonly involves both paraquat and diquat (DQ); DQ poisoning alone is less frequently reported, and especially rare in Japan. We present a case of fatal DQ poisoning after attempted suicide by ingesting DQ dibromide, requiring intensive care including hemodialysis (HD). Toxicological profiles of DQ, DQ metabolites, and bromide ion in serum were investigated relative to the course of treatment. Quantitative analyses were carried out by liquid chromatography/tandem mass spectrometry (LC-MS/MS) for DQ and its oxidative metabolites, and by capillary electrophoresis (CE) for bromide (Br-). Quantitated initial serum DQ concentration prior to HD#1 was 75 μg/mL. Following HD#1, DQ concentration dropped to 8.4 μg/mL, but re-elevated about 12 hours later (12 μg/mL). HD#2 lowered the DQ concentration to 1.5 μg/mL but again re-elevated prior to death (2.8 μg/mL). Serum Br- concentration pre-HD#1 was 493 μg/mL and dropped to 27-49 μg/mL after HD treatment. While HD treatment seemed to have reduced the DQ concentration significantly, re-elevation of the serum DQ level suggests that it was a temporary relief not enough to prevent the patient from going into multiple organ failure. Possibility of bromism was also investigated, as the ingested herbicide contained 33% DQ dibromide, thus Br- would have also been absorbed into the body along with DQ.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005709","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":"Oral fluid device performance in identifying amphetamine, methamphetamine, and cocaine use in Brazilian drivers.","authors":"Bruno Pereira Dos Santos, Juliana Nichterwitz Scherer, Patrícia Pacheco Viola, Bruna Govoni, Mailton Vasconcelos, Carolina Silveira Dalanhol, Gabriela Ramos Borges, Giovanna Cristiano de Gouveia, Ana Carolina Furiozo Arantes, Aline Franco Martins, José Luiz da Costa, Marilyn A Huestis, Flavio Pechansky","doi":"10.1093/jat/bkaf033","DOIUrl":"https://doi.org/10.1093/jat/bkaf033","url":null,"abstract":"<p><p>Stimulant use while driving is a high-risk factor for collisions and fatalities. In recent years, several strategies to curtail impaired driving were employed on highways, including on-site oral fluid testing. This study evaluated four roadside oral fluid testing devices (AquilaScan®, Dräger DrugTest®, Druglizer®, and DrugWipe®) for the detection of amphetamine, methamphetamine, and cocaine in oral fluid from Brazilian drivers. Overall, 8,985 screening tests were conducted, and LC-MS/MS analysis was performed on 46% of the oral fluid samples. Screening and confirmatory test results were compared considering the manufacturers' and Substance Abuse and Mental Health Services Administration's (SAMHSA) recommended cutoff concentrations. Performance reliability data are available for well-known oral fluid screening devices such as the Dräger DrugTest® or Securetec DrugWipe®, but most evaluations were based on highly prevalent cannabinoid results. In many cases, there were insufficient data to evaluate performance of other drug classes, including reliability data for amphetamines and cocaine that are presented here. Approximately, 3.0% of samples screened positive for amphetamine, 0.9% for methamphetamine, and 2.6% for cocaine. Efficiency was higher than 93.9% for all devices, but other parameters varied considerably, with sensitivity 56.4% to 100% and Positive Predictive Value (PPV) 4.2% to 87.1%. When considering the recommended minimum of 80% performance criteria suggested by the DRUID study, the Dräger DrugTest® was the only device to achieve satisfactory sensitivity, specificity, and efficiency for these stimulants at multiple evaluated cutoffs. Given the observed variability between devices, a detailed evaluation of the analytical performance of roadside oral fluid testing devices is advised before implementation in traffic enforcement actions.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005885","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":"Quantification of daridorexant, lemborexant and suvorexant in whole blood using liquid chromatography-tandem mass spectrometry.","authors":"Munchelou M Gomonit, Britni N Skillman","doi":"10.1093/jat/bkaf032","DOIUrl":"https://doi.org/10.1093/jat/bkaf032","url":null,"abstract":"<p><p>Suvorexant, lemborexant, and daridorexant are dual orexin receptor antagonists (DORAs) used to treat insomnia, offering a lower abuse potential due to their lack of gamma-aminobutyric acid activity compared to traditional sleep medications. Still, DORAs remain drugs of forensic interest due to their accessibility, long half-lives, and potential risk for next-day residual drowsiness, impaired motor coordination, and decreased alertness, which may feature prominently in cases of driving impairment or drug-facilitated sexual assault. Thus, developing analytical methods to detect these compounds, particularly the more novel lemborexant and daridorexant, is crucial for forensic toxicological testing. This study aimed to develop and validate an LC-MS/MS method for quantifying daridorexant, lemborexant, and suvorexant in blood. An acidic/neutral liquid-liquid extraction (LLE) using n-butyl chloride was optimized to isolate the three DORAs and the internal standard, suvorexant-d6, from bovine blood. All accuracy, precision and key validation parameters met acceptability requirements per ANSI/ASB 036. LLE recovery was >94%, with the calibration range between 0.25-500 ng/mL for all analytes. The LLOQ was 0.25 ng/mL. Matrix effects were -54.2% to 75.7%. Bias ranged between -10.9% to 8.8%, while %CV was <17.7%. Two-fold dilution integrity studies yielded a bias <-7.6%, with %CV <7.6%. Exogenous/endogenous interferences were negligible. Re-injection of the blank following the highest calibrator was free from carryover. Extracts were stable beyond 48 hours when stored at 4°C. A proof-of-concept study using authentic blood samples containing suvorexant, compared to previously reported concentrations, showed no consistent decrease over time, highlighting the need for further studies to determine optimal storage conditions for long-term stability. Although further studies are needed with authentic samples containing the more novel DORAs lemborexant or daridorexant, this validated method supports broader adoption in forensic toxicology, enhancing the detection and monitoring of these emerging sedative-hypnotics in forensic investigations.</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":"144008109","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}