Laura W Friederich, Mary E Cox, Brian E Hyson, Sandra C Bishop-Freeman
{"title":"Suspected North Carolina counterfeit pill-involved deaths, 2020–2022","authors":"Laura W Friederich, Mary E Cox, Brian E Hyson, Sandra C Bishop-Freeman","doi":"10.1093/jat/bkae027","DOIUrl":"https://doi.org/10.1093/jat/bkae027","url":null,"abstract":"The NC Office of the Chief Medical Examiner regularly assumes jurisdiction over deaths that are suspicious, unusual or unattended by a medical professional. In recent years, the presence of counterfeit pills is occasionally suggested by investigatory notes and/or scene findings that document reported consumption of prescription drugs, or prescription drugs on scene, which are not reflected in the final autopsy findings after toxicological analysis of the decedent’s blood samples. Counterfeit pill consumption is a major public health hazard worthy of attention from the forensic toxicology community. Seventy-five cases from January 2020 to December 2022 serve as a convenience sample of cases where prescription pills including formulations of alprazolam, oxycodone and hydrocodone were specifically referenced during the death scene investigation as recently consumed, yet an unexpected substance was found during toxicological analysis rather than the expected pharmaceutical drug. Of note, novel benzodiazepines detected included flualprazolam, etizolam, clonazolam metabolite (8-aminoclonazolam), bromazolam, flubromazolam and desalkylflurazepam. Decedents’ ages ranged from 16 to 69, across 33 different NC counties. Case notes indicated that eight of the decedents obtained pills through direct personal relationships, six decedents obtained them from “the street” and one decedent likely purchased pills online. Pills were largely consumed orally or through insufflation. Seven case reports contained indication that decedents knew or suspected the counterfeit nature of their pills. This study describes the context and characteristics of 2020–2022 suspected counterfeit pill-involved deaths in NC to further the understanding of the forensic science community, law enforcement partners, public health stakeholders and those potentially at risk through the consumption of counterfeit pills.","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":"11 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831716","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":"2-Fluorodeschloroketamine consumption: About two deaths and a case of self-mutilation","authors":"Salomé Riess, Marjorie Chèze, Aurelie Muckensturm, Nadine Klinger, Olivier Roussel, Vincent Cirimele","doi":"10.1093/jat/bkae021","DOIUrl":"https://doi.org/10.1093/jat/bkae021","url":null,"abstract":"2-Fluorodeschloroketamine (2-FDCK) is a new psychoactive substance (NPS), close to the ketamine structure. Few cases of 2-FDCK intake are described in the forensic literature, especially concerning death cases. We report here a case of self-mutilation (Case 1) and two forensic deaths linked to 2-FDCK consumption. The second case involved a man found dead in the street, having been stabbed. The third case was a man found dead following a suspected overdose and in an advanced state of putrefaction. For all three cases, biological fluids such as blood and urine were analyzed, as was hair for the two fatal cases. The aim of this study was to identify and quantify 2-FDCK and its main metabolites in different matrices. Biological fluids and hair were analyzed by liquid chromatography coupled with tandem mass spectrometry after decontamination and extraction. Seized products were analyzed by gas chromatography–mass spectrometry and assayed, when possible, by ultra-performance liquid chromatography with diode-array detection. 2-FDCK was detected and quantified in the peripheral blood of Cases 1, 2 and 3 (457, 758 and 5885 µg/L, respectively), as were its main metabolites nor-2-FDCK, dihydro-nor-2-FDCK and dihydro-2-FDCK. In the 1 cm long hair of Cases 2 and 3, 2-FDCK was also detected (approximately 4149 and 79824 pg/mg, respectively). Deschloroketamine (DCK) was found in the biological fluids of Cases 1, 2 and 3 (10, 8 and 350 µg/L, respectively), as well as in hair of Cases 2 and 3 (65 and around 8119 pg/mg, respectively). In Case 3, as a small bag containing DCK powder was seized from his home, we can assume that DCK was taken. On the contrary, to our knowledge, it has not been established that Case 2 took DCK alone, so we can assume that it may be the first case to report DCK from 2-FDCK metabolism in fluids as well as in hair.","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":"82 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140565967","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}
Robert Kronstrand, Markus Roman, Henrik Green, Michael T Truver
{"title":"Quantitation of hexahydrocannabinol (HHC) and metabolites in blood from DUID-cases","authors":"Robert Kronstrand, Markus Roman, Henrik Green, Michael T Truver","doi":"10.1093/jat/bkae030","DOIUrl":"https://doi.org/10.1093/jat/bkae030","url":null,"abstract":"Hexahydrocannabinol (HHC) was first reported in the EU in May 2022. HHC has three chiral carbon atoms, but only (6aR,9R,10aR)-HHC (9R-HHC) and (6aR,9S,10aR)-HHC (9S-HHC) have been encountered in HHC products. The goal of this study was to develop and validate a method for the quantitative analysis of 9R-HHC, 9S-HHC, 11-OH-9R-HHC, 9R-HHC-COOH, 9S-HHC-COOH, and 8-OH-9R-HHC. In addition, an objective was to investigate the immunochemical cross reactivity. Blood samples from DUID-cases screened positive for cannabis using ELISA and confirmed negative for tetrahydrocannabinol (THC), 11-hydroxy-THC, and THC-COOH were reanalyzed with a newly validated HHC method to investigate the presence of HHC and metabolites. The LC-MS/MS method was validated for matrix effects, lower limit of quantification (LLOQ), calibration model, precision, bias, and autosampler stability. Cross reactivity on an ELISA method was investigated separately for 9R-HHC-COOH and 9S-HHC-COOH at a concentration range between 5-200 ng/mL. The cross reactivity was found to be 120% for 9R-HHC-COOH and 48% for 9S-HHC-COOH. In the LCMSMS method 9R-HHC-COOH, 9S-HHC-COOH, and 11-OH-9R-HHC showed matrix effects less than 25% at both concentrations while 8-OH-9R-HHC, 9R-HHC, and 9S-HHC matrix effects exceeded 25% at both concentrations but showed good precision (<10% for both inter and between day) and low bias (<6%) in the further validation. The LLOQ was investigated and established at 0.2 ng/mL for all analytes except the carboxylated metabolites that had an LLOQ of 2.0 ng/mL. The upper limit of quantification was 20 and 200 ng/ml respectively. Reanalysis of cases (N=145) confirmed HHC and metabolites in 32 cases (22%). It was determined that the major metabolite in blood after administration of HHC was 9R-HHC-COOH followed by 11-OH-9R-HHC and that presumptive positive cases are caught by the routine ELISA screening for cannabis.","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":"102 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140565503","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}
Larissa K Karas, Courtney Patterson, Zachary J Fuller, Erin L Karschner
{"title":"Automated Extraction and LC-MS/MS Analysis of 11-Nor-9-carboxy-tetrahydrocannabinol Isomers and Prevalence in Authentic Urine Specimens","authors":"Larissa K Karas, Courtney Patterson, Zachary J Fuller, Erin L Karschner","doi":"10.1093/jat/bkae031","DOIUrl":"https://doi.org/10.1093/jat/bkae031","url":null,"abstract":"11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH) is the most frequently detected illicit drug metabolite in the military drug testing program. An increasing number of specimens containing unresolved Δ8-THCCOOH prompted the addition of this analyte to the Department of Defense (DoD) drug testing panel. A method was developed and validated for the quantitative confirmation of the carboxylated metabolites of Δ8- and Δ9-THC in urine samples utilizing automated pipette tip dispersive solid phase extraction and analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS). Analytes were separated isocratically over an 8.5 min runtime and detected on an MS/MS system equipped with an electrospray ionization source operating in negative mode. A single point calibrator (15 ng/mL) forced through zero demonstrated linearity from 3 to 1,000 ng/mL. Intra- and inter-day precision were ≤9.1% CV, and bias was within ±14.1% for Δ8-THCCOOH and Δ9-THCCOOH. No interferences were found after challenging the method with different over-the-counter drugs, prescription pharmaceuticals, drugs of abuse, and several cannabinoids and cannabinoid metabolites, including Δ1°-THCCOOH. Urine specimens presumptively positive by immunoassay (n=2939; 50 ng/mL Δ9-THCCOOH cutoff) were analyzed with this confirmation method. Specimens that contained Δ8-THCCOOH often had Δ9-THCCOOH above the 15 ng/mL cutoff. However, nearly one-third of the specimens analyzed were positive for Δ8-THCCOOH only. This manuscript describes the first validated automated extraction and confirmation method for Δ8- and Δ9-THCCOOH in urine that provides adequate analyte separation in urine specimens with extreme isomer abundance ratios.","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":"79 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140565442","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}
James Langston, Samuel Stump, Michael Filigenzi, Andriy Tkachenko, Jake Guag, Robert Poppenga, Wilson K Rumbeiha
{"title":"Extensive evaluation of a new LC-MS/MS method to quantify monofluoroacetate toxin in the kidney","authors":"James Langston, Samuel Stump, Michael Filigenzi, Andriy Tkachenko, Jake Guag, Robert Poppenga, Wilson K Rumbeiha","doi":"10.1093/jat/bkae032","DOIUrl":"https://doi.org/10.1093/jat/bkae032","url":null,"abstract":"Monofluoroacetate (MFA) is a highly lethal toxin which causes death by inhibiting cellular ATP production. The heart and brain are the primary target organs. Acute death is attributed to cardiac fibrillation and/or convulsions. Although it occurs naturally in some plants, a major source of animal intoxication is access to sodium monofluoroacetate (NaMFA) pesticide which continues to be a concern in the US and around the world despite restricted use in some countries including the US. There are also concerns about misuse of this pesticide for malicious poisoning. Currently, a tissue-based diagnostic method for NaMFA intoxication in animals is lacking. There is a critical need by the veterinary diagnostic community for a simple, sensitive, and reliable tissue-based diagnostic test to confirm NaMFA poisoning in animals. We have developed and extensively evaluated a sensitive novel LC-MS/MS method suitable for this purpose. The limits of detection (LOD) and limits of quantitation (LOQ) are 1.7 ng/g and 5.0 ng/g, respectively. The accuracy and precision met or exceeded expectations. The method performance was verified using incurred kidney obtained from animal diagnostic cases. This novel kidney-based method is now available for clinical use and can help with diagnostic purposes, including detecting potential issues related to animal foods.","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":"58 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140565498","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":"Evaluation of the Canadian approved drug screening equipment cut-off levels for tetrahydrocannabinol (THC).","authors":"Heather Copley, Angela Filbert, Kali Williams","doi":"10.1093/jat/bkae004","DOIUrl":"10.1093/jat/bkae004","url":null,"abstract":"<p><p>In 2018, Canada introduced roadside oral fluid (OF) screening devices, called Approved Drug Screening Equipment (ADSE), as an investigative tool in impaired driving investigations to detect tetrahydrocannabinol (THC), cocaine and/or methamphetamine in drivers. In this work, we compare the detection and concentration of THC in blood samples collected from suspected impaired drivers that tested positive at the roadside for THC on an ADSE. The two ADSEs that were utilized were the Dräger DrugTest® 5000 (DDT) and the Abbott SoToxa™ (SoToxa), both configured with a THC OF concentration cut-off concentration of 25 ng/mL. Blood samples were screened for cannabinoids using immunoassay and positive results were followed up by confirmation/quantitation of THC by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS-MS). A total of 230 cases were available where a blood sample was collected from a suspected impaired driver subsequent to a positive THC screen result on an ADSE. The blood samples were taken an average of 1.4 hours (range = 9 minutes to 3.2 hours) after the ADSE test. THC was confirmed in 98% of blood samples with concentrations across all samples ranging from not detected (cut = off 0.5 ng/mL) to greater than 20 ng/mL. Further, 90% of the blood samples had a THC concentration of 2.0 ng/mL (the lower per se limit in Canada) or greater. A positive ADSE test of a suspected impaired driver may predict that the driver has a detectable level of THC in their blood, and there is a high likelihood that the THC blood concentration is 2.0 ng/mL or higher. Hence, ADSE may be a useful tool for law enforcement and aid in the development of grounds to believe that a driver is operating a conveyance with a THC concentration exceeding Canadian per se limits.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"165-170"},"PeriodicalIF":2.5,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722641","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}
Svante Vikingsson, Ruth E Winecker, David J Kuntz, Michael Clark, Martin Jacques, E Dale Hart, Eugene D Hayes, Ronald R Flegel, Lisa S Davis
{"title":"Fentanyl as a marker of illicit drug use in morphine-positive urine specimens from workplace drug testing.","authors":"Svante Vikingsson, Ruth E Winecker, David J Kuntz, Michael Clark, Martin Jacques, E Dale Hart, Eugene D Hayes, Ronald R Flegel, Lisa S Davis","doi":"10.1093/jat/bkae003","DOIUrl":"10.1093/jat/bkae003","url":null,"abstract":"<p><p>Total morphine is an important urinary marker of heroin use but can also be present from prescriptions or poppy seed ingestion. In specimens with morphine concentrations consistent with poppy seed ingestion (<4,000 ng/mL), 6-acetylmorphine has served as an important marker of illicit drug use. However, as illicit fentanyl has become increasingly prevalent as a contaminant in the drug supply, fentanyl might be an alternative marker of illicit opioid use instead of or in combination with 6-acetylmorphine. The aim of this study was to quantify opiates, 6-acetylmorphine, fentanyl and fentanyl analogs in 504 morphine-positive (immunoassay 2,000 ng/mL cutoff) urine specimens from workplace drug testing. Almost half (43%) of morphine-positive specimens had morphine concentrations below 4,000 ng/mL, illustrating the need for markers to differentiate illicit drug use. In these specimens, fentanyl (22% co-positivity) was more prevalent than 6-acetylmorphine (12%). Co-positivity of 6-acetylmorphine and semi-synthetic opioids increased with morphine concentration, while fentanyl prevalence did not. In 110 fentanyl-positive specimens, the median norfentanyl concentration (1,520 ng/mL) was 9.6× higher than the median fentanyl concentration (159 ng/mL), illustrating the possibility of using norfentanyl as a urinary marker of fentanyl use. The only fentanyl analog identified was para-fluorofentanyl (n = 50), with results from most specimens consistent with para-fluorofentanyl contamination in illicit fentanyl. The results confirm the use of fentanyl by employees subject to workplace drug testing and highlight the potential of fentanyl and/or norfentanyl as important markers of illicit drug use.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"185-190"},"PeriodicalIF":2.5,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650812","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":"Dubowski's stages of alcohol influence and clinical signs and symptoms of drunkenness in relation to a person's blood-alcohol concentration-Historical background.","authors":"Alan Wayne Jones","doi":"10.1093/jat/bkae008","DOIUrl":"10.1093/jat/bkae008","url":null,"abstract":"<p><p>This article traces the origin of various charts and tables delineating the stages of alcohol influence in relation to the clinical signs and symptoms of drunkenness and a person's blood-alcohol concentration (BAC). In forensic science and legal medicine, the most widely used such table was created by Professor Kurt M. Dubowski (University of Oklahoma). The first version of the Dubowski alcohol table was published in 1957, and minor modifications appeared in various articles and book chapters until the final version was published in 2012. Seven stages of alcohol influence were identified including subclinical (sobriety), euphoria, excitement, confusion, stupor, alcoholic coma and death. The BAC causing death was initially reported as 0.45+ g%, although the latest version cited a mean and median BAC of 0.36 g% with a 90% range from 0.21 g% to 0.50 g%. An important feature of the Dubowski alcohol table was the overlapping ranges of BAC for each of the stages of alcohol influence. This was done to reflect variations in the physiological effects of ethanol on the nervous system between different individuals. Information gleaned from the Dubowski table is not intended to apply to any specific individual but more generally for a population of social drinkers, not regular heavy drinkers or alcoholics. Under real-world conditions, much will depend on a person's age, race, gender, pattern of drinking, habituation to alcohol and the development of central nervous tolerance. The impairment effects of ethanol also depend to some extent on whether observations are made on the rising or declining phase of the blood-alcohol curve (Mellanby effect). There will always be some individuals who do not exhibit the expected behavioral impairment effects of ethanol, such as regular heavy drinkers and those suffering from an alcohol use disorder.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"131-140"},"PeriodicalIF":2.5,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706760","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}
Katie Diekhans, Jihau Yu, Megan Farley, Luke N Rodda
{"title":"Analysis of over 250 novel synthetic opioids and xylazine by LC-MS-MS in blood and urine.","authors":"Katie Diekhans, Jihau Yu, Megan Farley, Luke N Rodda","doi":"10.1093/jat/bkae009","DOIUrl":"10.1093/jat/bkae009","url":null,"abstract":"<p><p>Novel Synthetic Opioids (NSO) are frequently found in postmortem (PM) and human performance (HP) forensic toxicology casework, resulting in impairment and fatal overdoses. Developing a broad NSO method benefits public health, as it can be used to identify trends in potent opioid use to develop risk management programs. This project aimed to design a comprehensive, rapid and routine method for the selective analysis of over 250 novel synthetic opioids in blood and urine. This method rapidly extracted 150 µL of blood or urine via protein precipitation followed by size-exclusion filtration, evaporation and reconstitution. Separation and data acquisition were achieved on a 12 min LC-MS-MS method using an F5 column. Data processing was expedited with a custom built-in query created in-house that automated processing and enhanced quality assurance. Validation according to ASB/ANSI Standard 036 was performed and applicability of the method was assessed using proficiency test and authentic casework samples. Assessed in blood and urine qualitatively were 261 unique analytes including fentanyl analogs (fentalogs), nitazenes and other miscellaneous synthetic opioids. As 59 isomeric target analytes were placed into groups due to co-elution, there were 202 distinct acquired targets or target - groups. To demonstrate applicability, 27 proficiency test blood samples received over an approximate 4-year period were analyzed with 126 expected results assessed comprising 25 unique target analytes. Additionally, 617 fatal accidental overdoses within San Francisco in 2022 were retroactively analyzed by this method with almost 10% of cases containing a new NSO substance(s). Such trends and NSO substances were previously unknown in this community.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"150-164"},"PeriodicalIF":2.5,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068373","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}
Sofia Jonasson, Roger Magnusson, Håkan Wingfors, Åsa Gustafsson, Gregory Rankin, Linda Elfsmark, Lina Mörén
{"title":"Potential exhaled breath biomarkers identified in chlorine-exposed mice.","authors":"Sofia Jonasson, Roger Magnusson, Håkan Wingfors, Åsa Gustafsson, Gregory Rankin, Linda Elfsmark, Lina Mörén","doi":"10.1093/jat/bkae007","DOIUrl":"10.1093/jat/bkae007","url":null,"abstract":"<p><p>Exhaled breath (EB) contains various volatile organic compounds (VOCs) that can indicate specific biological or pathological processes in the body. Analytical techniques like gas chromatography-mass spectrometry (GC-MS) can be used to detect and measure these exhaled biomarkers. In this study, the objective was to develop a non-invasive method of EB sampling in animals that were awake, as well as to analyze EB for volatile biomarkers specific for chlorine exposure and/or diagnostic biomarkers for chlorine-induced acute lung injury (ALI). To achieve this, a custom-made sampling device was used to collect EB samples from 19 female Balb/c mice. EB was sampled both pre-exposure (serving as internal control) and 30 min after exposure to chlorine. EB was collected on thermal desorption tubes and subsequently analyzed for VOCs by GC-MS. The following day, the extent of airway injury was assessed in the animals by examining neutrophils in the bronchoalveolar lavage fluid. VOC analysis revealed alterations in the EB biomarker pattern post-chlorine exposure, with eight biomarkers displaying increased levels and six exhibiting decreased levels following exposure. Four chlorinated compounds: trichloromethane, chloroacetone, 1,1-dichloroacetone and dichloroacetonitrile, were increased in chlorine-exposed mice, suggesting their specificity as chlorine EB biomarkers. Furthermore, chlorine-exposed mice displayed a neutrophilic inflammatory response and body weight loss 24 h following exposure. In conclusion, all animals developed an airway inflammation characterized by neutrophil infiltration and a specific EB pattern that could be extracted after chlorine exposure. Monitoring EB samples can readily and non-invasively provide valuable information on biomarkers for diagnosis of chlorine-induced ALI, confirming chlorine exposures.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"171-179"},"PeriodicalIF":2.5,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706761","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}