Journal Of Analytical Toxicology[JOURNAL]
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200 papers
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.
Kusano M, Iwamuro Y, Terayama T … +3 more , Murakami T, Fujishiro M, Matsuyama TA
J Anal Toxicol · 2025 Sep · PMID 40296681 · Publisher ↗
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 ingest...
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 haemodialysis (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 for bromide (Br-). The 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.
Oral fluid device performance in identifying amphetamine, methamphetamine, and cocaine use in Brazilian drivers.
Dos Santos BP, Scherer JN, Viola PP … +10 more , Govoni B, Vasconcelos M, Dalanhol CS, Borges GR, de Gouveia GC, Arantes ACF, Martins AF, da Costa JL, Huestis MA, Pechansky F
J Anal Toxicol · 2025 Sep · PMID 40279174 · Publisher ↗
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...
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, 8985 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 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 56.4-100% and positive predictive value 4.2-87.1%. When considering the recommended minimum of 80% performance criteria suggested by the Driving Under the Influence of Drugs, Alcohol, and Medicines 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.
Quantification of daridorexant, lemborexant, and suvorexant in whole blood using liquid chromatography-tandem mass spectrometry.
Gomonit MM, Skillman BN
J Anal Toxicol · 2025 Sep · PMID 40269529 · Publisher ↗
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 traditiona...
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 and 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% and 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 h 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 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.
North America laboratory survey data for drug testing in drug-impaired driving and traffic fatality investigations.
D'Orazio AL, Mohr ALA, Chan-Hosokawa A … +8 more , Harper C, Huestis MA, Kerrigan S, Limoges JF, Miles AK, Scarneo CE, Scott KS, Logan BK
J Anal Toxicol · 2025 Sep · PMID 40269510 · Publisher ↗
In 2004, the National Safety Council's Alcohol, Drugs, and Impairment Division set out to provide guidance for the standardization of laboratory testing practices in driving under the influence of drugs and fatal motor v...
In 2004, the National Safety Council's Alcohol, Drugs, and Impairment Division set out to provide guidance for the standardization of laboratory testing practices in driving under the influence of drugs 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 USA and Canada. Based on the 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 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 result is at or above a certain concentration, which further hinders the understanding of the drug-impaired driving problem. Delta-9-Tetrahydrocannabinol and/or metabolites remained the most prevalent drug reported by laboratories, followed by stimulants.
Hydroxyzine in impaired driving investigations.
Bierly JJ, D'Orazio AL
J Anal Toxicol · 2025 Sep · PMID 40269504 · Publisher ↗
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 (CNS) depressant effects s...
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 (CNS) depressant 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 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. 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.
Preparation and stability characterization of flavour ingredients in E-liquids for preclinical assessment of electronic nicotine delivering system products: a case study of 38 flavour ingredients in a single mixture.
Miller JH, Hurst TJ, Shah NH … +10 more , Zhang J, Frauendorfer F, Guy P, Diana P, Glabasnia A, Biasioli M, Hoeng J, Sciuscio D, Vanscheeuwijck P, Lee KM
J Anal Toxicol · 2025 Sep · PMID 40265589 · Full text
E-vapour products generate aerosols typically containing nicotine, flavour ingredients, and aerosol formers (propylene glycol and vegetable glycerine). While many flavour ingredients are 'generally recognized as safe (GR...
E-vapour products generate aerosols typically containing nicotine, flavour ingredients, and aerosol formers (propylene glycol and vegetable glycerine). While many flavour 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 route. Due to the large number of available ingredients and potential combinations used to create e-liquids, toxicological and analytical evaluation of each flavour 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 'preblends' prior to making a test formulation, containing 38 flavour ingredients as an example case, ahead of preclinical toxicity testing. We used the preblends to simplify the preparation and the characterization of test formulations, establishing the stability criteria for the subsequent toxicity testing. We prepared preblends by dividing the 38 flavour ingredients into five preblend groups based on structural moiety, solubility, and chemical reactivity. These preblends were mixed to make two different 'final' test formulations (containing all 38 flavour ingredients with and without nicotine). We evaluated the stability of the preblends and the two test formulations prior to the subsequent in vivo inhalation studies. Based on the analytical assessment, all the preblends were stable up to 4 weeks at 0°C-4°C. When all preblends 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°C-4°C. These stability results were used to set the frequency of preparing the test formulations for the in vivo inhalation studies, ensuring stability of test materials prior to the biological testing.
Synthetic cannabinoid receptor agonists in oral fluid: development of a dispersive liquid-liquid microextraction method with liquid chromatography-mass spectrometry detection.
Bombana HS, de Paula Meirelles G, de Oliveira RA … +2 more , Leyton V, Yonamine M
J Anal Toxicol · 2025 Sep · PMID 40176730 · Publisher ↗
Synthetic cannabinoid receptor agonists (SCRA) comprise a class of new psychoactive substances (NPS) that rank second in terms of notified substances to the United Nations Office on Drugs and Crime. Moreover, SCRA are th...
Synthetic cannabinoid receptor agonists (SCRA) comprise a class of new psychoactive substances (NPS) that rank second in terms of notified substances to the United Nations Office on Drugs and Crime. Moreover, SCRA are the most prevalent NPS in Brazilian territory. Given the risks they pose to public health, there is a pressing need to develop simple and rapid sample preparation methods in alternative biological matrices that are easy to handle and collect, such as oral fluid (OF). In this study, dispersive liquid-liquid microextraction was employed to determine 12 SCRAs in OF. For 200 µl of the sample (mixture of OF and Quantisal™ buffer), 200 µl of ice-cold acetonitrile was used as the dispersive solvent, and 100 µl of ethyl acetate was used as the extraction solvent. The limits of detection ranged from 0.5 to 2 ng/mL, while the limits of quantification were 2 ng/mL for ADB-FUBIATA and 1 ng/mL for the other analytes. The working range was 1-100 ng/mL, except for ADB-FUBIATA, which had a range of 2-100 ng/mL. The coefficients of variation for quantified analytes were <11.3% for within-run precision, <12.6% for between-run precision, and <15.8% for accuracy across all controls. The developed method was applied to six suspected samples, and one sample yielded a positive result with 39.9 ng/mL of MDMB-4en-PINACA, the most prevalent SCRA in São Paulo State, Brazil.
Toxicological detection of the new psychoactive substances MDPHP and MDPHpP in human urine samples by elucidation of their urinary metabolites using gas chromatography-mass spectrometry.
Brueckner I, Welter-Luedeke J, Gutjahr-Ruhland C … +2 more , Graw M, Paul LD
J Anal Toxicol · 2025 May · PMID 40130363 · Publisher ↗
The continuous emergence of new psychoactive substances on the illicit drug market provides challenges for forensic and clinical analytics. Reliable detection of previous ingestion of these drugs in human urine samples r...
The continuous emergence of new psychoactive substances on the illicit drug market provides challenges for forensic and clinical analytics. Reliable detection of previous ingestion of these drugs in human urine samples requires elucidation of target metabolites and, in the case of gas chromatography-mass spectrometry (GC-MS), the knowledge of their derivatized mass spectra. The study presented here focused on the two pyrrolidinophenones 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) and 3,4-methylenedioxy-α-pyrrolidinoheptanophenone (MDPHpP), which could be identified in 25 and 3 authentic cases, respectively. Using a standard analytical procedure by means of full-scan GC-MS after acid hydrolysis and acetylation, phase I metabolites of both substances were identified in authentic urine samples by elucidation of their mass spectral fragmentation patterns. The postulated phase I metabolic steps of MDPHP and MDPHpP comprised demethylenation followed by methylation of the methylenedioxy moiety, oxidation of the pyrrolidine ring, N,N-bisdealkylation of the pyrrolidine ring to its primary amine, and hydroxylation of the aliphatic side chain. Various combinations were detected. Acetylated mass spectra of the metabolites were provided for both substances. The analogy in mass fragmentation of the proposed metabolites for the homologous parent compounds indicated a high plausibility. Based on the frequency of occurrence and abundances of the metabolites in the urine samples, target analytes for both substances and base peak fragment ions for specific mass search could be recommended for the mentioned procedure: m/z 140, 154, and 86 for MDPHP and m/z 154, 168, and 100 for MDPHpP. The study could support the detection of these new substances in forensic and clinical cases.
Comprehensive LC-MS-MS analysis of THC isomers, analogs, homologs, and metabolites in blood and urine.
Muir LS, Doumit SE, Seither JZ … +3 more , Knittel JL, Walterscheid JP, Karschner EL
J Anal Toxicol · 2025 May · PMID 40098275 · Publisher ↗
The legalization of hemp and the commercialization of hemp-based extracts have resulted in numerous cannabinoids appearing in consumer products. Although human pharmacological data are lacking for many of these isomers,...
The legalization of hemp and the commercialization of hemp-based extracts have resulted in numerous cannabinoids appearing in consumer products. Although human pharmacological data are lacking for many of these isomers, analogs, and homologs of delta-9-tetrahydrocannabinol (Δ9-THC), these cannabinoids may be capable of inducing cannabimimetic effects. Structural similarities also pose unique analytical challenges due to overlapping retention times and ion transitions used to distinguish between various parent drugs and metabolites. Therefore, traditional cannabinoid assays containing Δ9-THC, 11-hydroxy-Δ9-THC (11-OH-Δ9-THC), and 11-nor-9-carboxy-Δ9-THC (Δ9-THCCOOH) are no longer sufficient to confront this new threat to public safety. A new method has been developed and validated to quantitatively confirm Δ8- and Δ9-THC, their hydroxylated and carboxylated metabolites, and 9(R)- and 9(S)-hexahydrocannabinol (HHC) stereoisomers in blood and qualitatively identify these analytes in urine. This method is also capable of qualitatively confirming Δ9,11-THC (exo-THC), HHCCOOH, Δ6a,10a-THCCOOH/Δ10-THCCOOH, and Δ8 and Δ9 THC homologs including tetrahydrocannabivarin (THCV), tetrahydrocannabutol (THCB), tetrahydrocannabihexol (THCH; Δ8-THCH in urine only), tetrahydrocannabiphorol (THCP), THC-C8, as well as 9(R)- and 9(S)-hexahydrocannabiphorol (HHCP) in blood and urine. Limits of detection were 1 ng/mL for non-carboxylated analytes and 5 ng/mL for carboxylated analytes. Calibration curves for parent and hydroxylated THC isomers and HHC stereoisomers were 1 to 50 ng/mL, whereas calibration curves for the carboxylated THC isomers were 5-250 ng/mL. This method separates all analytes of interest from potential synthesis byproducts such as Δ8-iso-THC, Δ4(8)-iso-THC, and exo-THC. Unambiguous identification of these cannabinoids will increase forensic toxicology reporting accuracy while navigating the changing landscape of cannabis regulation and product formulation.
Testing for trazodone, an antidepressant, in hair collected from horses.
Kintz P, Baudry M, Gheddar L
J Anal Toxicol · 2025 Jul · PMID 40088067 · Publisher ↗
Trazodone, a medicine registered for human, is a serotonin agonist-antagonist. At low dose, the drug is sedative due to its antagonist properties. At high dose, it is an agonist with anxiolytic and antidepressant actions...
Trazodone, a medicine registered for human, is a serotonin agonist-antagonist. At low dose, the drug is sedative due to its antagonist properties. At high dose, it is an agonist with anxiolytic and antidepressant actions. Trazodone can be administered to the horse to reduce anxiety. However, according to the antidoping rules for horses, the presence of trazodone in blood or urine is considered as a violation, which will produce a suspension of both the athlete and the horse as the drug is listed banned on the International Federation of Horseracing Authorities prohibited substances list. As a hair test can provide more evidence or supplementary information to an adverse analytical finding or to document drug exposure, our forensic laboratory received two specimens with a request for trazodone identification. After mane collection, trazodone was analysed by a new LC-MS/MS method involving pH 9.5 borate buffer overnight incubation of 20 mg of specimen in presence of clozapine-d4 used as internal standard, followed by solvents extraction. Linearity was verified from 1 to 100 pg/mg (R2 = 0.9967). Limit of detection of the method was 0.1 pg/mg. Trazodone was measured at 0.4 pg/mg in the mane of a horse suspended after an antidoping violation. In a case of hidden administration, trazodone was identified at 9 and 24 pg/mg in two consecutive mane hair segments. Although no controlled study allows interpretation, particularly about the frequency of exposure and the dose that entered in the body, this is the first evidence that trazodone can be incorporated in the mane of horses.
The rising trend of MDPHP consumption: an Italian snapshot.
La Maida N, Aquilina V, Vaiano F … +7 more , Cavallo M, Locatelli CA, Mannaioni G, Arillotta D, Pichini S, Di Trana A, Graziano S
J Anal Toxicol · 2025 Jul · PMID 40088058 · Publisher ↗
Synthetic cathinones (SCs) were confirmed as the second most prevalent class of New Psychoactive Substances (NPS) in 2024, underscoring their widespread availability and use. Notably, the SCs seizure and related intoxica...
Synthetic cathinones (SCs) were confirmed as the second most prevalent class of New Psychoactive Substances (NPS) in 2024, underscoring their widespread availability and use. Notably, the SCs seizure and related intoxication cases increased within the European Union, involving mostly 3-chloromethcathinone, 3-methylmethcathinone, 2-methylmethcathinone, and N-ethylnorpentedrone. Italy has observed a distinct trend, with methylendioxy pyrrolidinohexanophenone (MDPHP) emerging as a significant concern. This technical note aims to provide a comparative analysis of the most recent data concerning the emergence and the spread of MDPHP in Italy. Data from the National Early Warning System on Drugs indicate that the total amount of seized MDPHP increased from 2021 to 2024. In 2023, MDPHP-related intoxication cases peaked at 47, considering either alone or in combination with other drugs, followed by a slight decrease in 2024. In Italy, MDPHP seems to dominate the Italian black market of SCs and with two fatalities reported. This increased demand for MDPHP raises health concerns, indicating the necessity to enhance drug-related harm reduction services and improve a multidisciplinary network that provides data for understanding the complex phenomenon of NPS.
Quantification of phosphatidylethanol 16:0/18:1 in blood using supercritical fluid chromatography-tandem mass spectrometry.
Gomonit MM, Roman M, Skillman BN … +2 more , Truver MT, Kronstrand R
J Anal Toxicol · 2025 May · PMID 40085069 · Publisher ↗
Phosphatidylethanol (PEth) consists of phospholipids synthesized in erythrocyte cell membranes in the presence of ethanol and serves as a sensitive and specific indicator of alcohol consumption. Further research on PEth...
Phosphatidylethanol (PEth) consists of phospholipids synthesized in erythrocyte cell membranes in the presence of ethanol and serves as a sensitive and specific indicator of alcohol consumption. Further research on PEth formation, degradation, and stability in postmortem (PM) samples would support its routine application in forensic toxicology. A supercritical fluid chromatography-tandem mass spectrometry (SFC-MS-MS) method was developed and validated to quantify PEth 16:0/18:1 in blood. PEth 16:0/18:1 was extracted from blood (0.25 g) using an 8:2 (v/v) heptane:2-propanol mixture. Method validation results met American National Standards Institute/Academy Standards Board 036 guidelines. Recovery was >48%, and matrix effects were <20%. The linear range was 10-2500 ng/g, and lower limit of quantification was 10 ng/g. Bias was ±17.7%, and precision was <17.1% for all quality control levels. Carryover, endogenous, and exogenous interferences were negligible. Extracts were stable beyond 72 hours. In a proof-of-concept study reanalyzing 35 PM case samples, PEth concentrations ranged between 32.6 to 2476 ng/g. Short-term stability studies showed that fortified bovine blood (200 ng/g) preserved with 0.4% sodium fluoride (NaF) stored at room temperature had a 6.6% concentration drop after 48 hours, while blood stored at 4°C decreased by 13.5% over 14 days. Additionally, human PEth-positive blood preserved with 0.4% NaF showed a 6.7% decrease in in vivo PEth concentrations compared to a 17.5% decrease in heparin-preserved blood after 14 days at 4°C, supporting the use of 0.4% NaF in reducing PEth degradation over time. An in vitro model was also developed to simulate early PM PEth changes. Results found that PEth formation occurred in an ethanol concentration-dependent manner with minimal degradation, and considerations should be taken when interpreting PEth concentrations in cases with long PM interval, and if the decedent had a high blood alcohol concentration level and was left at elevated temperatures. This is the first SFC-MS-MS method successfully developed and validated for the analysis of PEth in PM samples.
Green liquid-liquid microextraction for quantification of ketamine and metabolites in human urine by gas chromatography-mass spectrometry.
Yang HH, Kao CS, Lua AC … +1 more , Chou TY
J Anal Toxicol · 2025 May · PMID 40066987 · Publisher ↗
This study aimed to develop and validate a green method for the detection of ketamine and its metabolites in human urine samples and subsequently determine which metabolite is more suitable for judgment of ketamine abuse...
This study aimed to develop and validate a green method for the detection of ketamine and its metabolites in human urine samples and subsequently determine which metabolite is more suitable for judgment of ketamine abuse. Ketamine and its metabolites were extracted from urine samples with 1-undecanol using liquid-liquid microextraction based on the solidification of floating organic droplet extraction. The extracts were directly analyzed using gas chromatography-mass spectrometry (GC-MS) without derivatization. The sample pretreatment procedure prior to GC-MS analysis was simple, fast, and required little solvent consumption. Parameters that affect the extraction efficiency, including pH of the urine sample and centrifugation speed, were optimized. Under the optimized conditions, the limits of detection for norketamine, dehydronorketamine, and ketamine were 1.5, 1.7, and 1.0 ng/mL, respectively. The method was used to analyze eight real urine samples from drug abusers and exhibited acceptable accuracy and precision. By analyzing real samples, this study revealed that detection of dehydronorketamine in urine samples for the judgment of ketamine abuse may be more suitable than detection of norketamine or ketamine. The method used in this study addresses the need for green analytical techniques in toxicology.
Toxicological and demographic profiles of phencyclidine-impaired driving cases in Houston: updates from the 2019 to 2023 data.
Lee D, Corral SR, Duvall C … +1 more , Stout P
J Anal Toxicol · 2025 May · PMID 40045593 · Publisher ↗
Phencyclidine (PCP) is a dissociative anesthetic harmful to road traffic safety as the drug may impair driving performance by inducing adverse effects such as sedation, ataxia, agitation, disorientation, and confusion. H...
Phencyclidine (PCP) is a dissociative anesthetic harmful to road traffic safety as the drug may impair driving performance by inducing adverse effects such as sedation, ataxia, agitation, disorientation, and confusion. Houston Forensic Science Center previously reported toxicological and demographic characteristics of PCP-impaired driving cases in Houston from 2013 to 2018 and presently reports the 2019-23 cases. The blood samples collected from suspect drivers were analyzed for alcohol and drugs and those positive for PCP at the reporting limit of 5 ng/mL were included in the study (n = 1375). The drivers had the median (mean, range) PCP concentration of 45 (49, 5-170) ng/mL and were mostly males (77%) and black (89%) with the mean age of 40 years. More than half of the drivers (59%) were polydrug users with cannabinoids being the most frequently detected (39%), followed by cocaine/metabolites (15%) and ethanol (10%). Compared to our previous findings and other studies, the PCP concentration distributions and concurrent drug profiles of the drivers were remarkably consistent despite multiple changes in the drug market over the years; their demographics also remained comparable except for the mean age, which continued to increase. Continual surveillance of PCP-impaired driving cases is important to identify risk groups and aid in reducing this hazardous driving behavior, so prevalent and persistent in the city of Houston.
HIV combination drug therapies: development and validation of an LC-MS-MS method for simultaneous quantitation of abacavir, dolutegravir, and lamivudine in rat matrices in support of toxicology studies.
Silinski MAR, Gilliam JA, Apoian J … +3 more , Fletcher BL, Fernando RA, Waidyanatha S
J Anal Toxicol · 2025 May · PMID 40036775 · Full text
Abacavir (ABC), Dolutegravir (DTG), and Lamivudine (3TC) are part of a fixed-dose combination medication for the treatment of HIV. The three drugs offer different but complementary mechanisms of action by inhibiting reve...
Abacavir (ABC), Dolutegravir (DTG), and Lamivudine (3TC) are part of a fixed-dose combination medication for the treatment of HIV. The three drugs offer different but complementary mechanisms of action by inhibiting reverse transcriptase and integrase, and ultimately inhibiting HIV replication. Due to the lack of information regarding long-term safety following in utero exposure, we are evaluating potential toxicity to offspring following in utero exposure to this combination therapy in Hsd:Sprague Dawley®SD® (HSD) rats, including cardiovascular toxicity and neurotoxicity. Generating internal exposure data are integral to putting toxicological findings into context. The objective of this work was to develop and validate a method to simultaneously quantitate ABC, DTG, and 3TC in rat matrices following exposure to this combination. The method used protein precipitation of plasma, fetal, placental, brain, or heart homogenate, followed by ultra-performance liquid chromatography-tandem mass spectrometry. In adult Sprague Dawley rat plasma, the method was linear (r ≥ 0.99) over the range 10/15/5 to 10,000/15,000/5000 ng/mL for ABC/DTG/3TC and recovery was ≥92% for all three analytes at all concentration levels. The limits of detection were 2.22, 3.69, and 0.978 ng/mL for ABC, DTG, and 3TC, respectively. Intra- and inter-day precision was ≤8.7% relative standard deviation (RSD), and relative error (RE) ≤±12.0% for standards prepared at 20/30/10, 400/600/200, and 5000/7500/2500 ng/mL. Matrix standards as high as 40/60/20 µg/mL could be diluted into the calibration range (RE≤±3.5% and RSD ≤2.4%). The method was evaluated for HSD rat maternal plasma and fetal, placental, brain, and heart homogenates (mean RE ≤±15.0% and RSD ≤8.6%). Analyte stability was demonstrated in extracted plasma for 2 days at different temperatures, and in various matrices stored at -80°C for at least 32 days (80-113% of Day 0 concentrations). These data demonstrate that this simple and efficient method is suitable for quantitation of ABC, DTG, and 3TC in rat matrices generated from toxicology studies. The method can easily be adapted to other biological matrices and species (e.g. human).
Analysis of (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol and (-)-11-nor-9-carboxy-Δ8-tetrahydrocannabinol in hair from a school-age population.
Paulsen RB, Stowe GN, Schaffer MI … +1 more , Krohn N
J Anal Toxicol · 2025 Apr · PMID 40036755 · Publisher ↗
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...
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.
Brain concentrations and brain-blood ratios of amitriptyline and nortriptyline in forensic postmortem cases.
van der Meer MZ, Rasmussen BS, Nedahl M … +1 more , Nielsen MKK
J Anal Toxicol · 2025 Apr · PMID 40036614 · Full text
Concentrations of amitriptyline and nortriptyline in postmortem blood samples may not accurately reflect the concentrations at the time of death due to postmortem redistribution or degradation. The brain is suggested as...
Concentrations of amitriptyline and nortriptyline in postmortem blood samples may not accurately reflect the concentrations at the time of death due to postmortem redistribution or degradation. The brain is suggested as an alternative matrix since it is less subjected to postmortem redistribution and more protected against trauma and putrefaction, but reference concentrations in brain tissue are scarce. In this study, we aimed to provide concentrations in brain tissue and brain-blood ratios in 53 postmortem cases, where amitriptyline and/or nortriptyline were detected. To establish reference levels, each case was assigned to one of three classes according to the cause of death: (i) lethal intoxication by the sum of amitriptyline and nortriptyline or nortriptyline alone, (ii) lethal intoxication by the drugs in combination with other drugs, and (iii) the cause of death was not influenced by amitriptyline and/or nortriptyline. A positive correlation between blood and brain concentrations was found with a Spearman coefficient of 0.98. In 42 cases, where both drugs were detected, the 10-90 percentiles in brain tissue ranged from 0.17-9.1 mg/kg (median: 0.78 mg/kg) for amitriptyline and 0.22-5.0 mg/kg (median: 1.43 mg/kg) for nortriptyline across all classes. In 11 cases where only nortriptyline was detected, the percentiles ranged from 0.32-7.2 mg/kg (median: 0.28 mg/kg) in brain tissue. A median brain-blood ratio of 3.4 was found for amitriptyline, 8.5 for nortriptyline as a metabolite of amitriptyline and 9.7 for nortriptyline as an individual ingested drug. No significant difference was found between the different classes. The obtained brain concentrations and brain-blood ratio can contribute to the alternative or complementary use of brain tissue for future toxicological investigations.
Identification of 4F-MDMB-BICA using a molecular network strategy in a case of severe poisoning with coma.
Caré W, Magny R, Vodovar D … +5 more , Saint-Léger FB, Langrand J, Laborde-Castérot H, Labat L, Houzé P
J Anal Toxicol · 2025 May · PMID 40036602 · Publisher ↗
Synthetic cannabinoids remain one of the most important groups of new psychoactive substances and are responsible for many cases of poisoning in Europe. Deaths from acute 4F-MDMB-BICA poisoning have recently been reporte...
Synthetic cannabinoids remain one of the most important groups of new psychoactive substances and are responsible for many cases of poisoning in Europe. Deaths from acute 4F-MDMB-BICA poisoning have recently been reported. Severe poisonings may be underreported because 4F-MDMB-BICA is not routinely screened for in most forensic and toxicology laboratories. We report the case of a young man in France who presented with poisoning after orally consuming a powdered substance sold online as an opioid. The coma required intensive care unit management with emergent chest tube insertion and mechanical ventilation. The outcome was favorable with no sequelae due to early medical care. In the absence of remaining product and preserved urine samples, qualitative toxicological screening was performed on plasma, cerebrospinal fluid, and a hair strand. Using ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry and a molecular network data processing strategy, 4F-MDMB-BICA and two of its metabolites were identified only in plasma and cerebrospinal samples. These results were consistent with a single exposure. The identification of the substance consumed was crucial because of discrepancy between the symptoms observed and those expected after presumed exposure. Identification of 4F-MDMB-BICA and two of its metabolites was achieved in early plasma and cerebrospinal fluid samples. This documented case is helping to improve knowledge of 4F-MDMB-BICA poisoning, which could be an emerging public health issue.
A comparison of vitreous fluid and blood matrices in postmortem drug analysis.
Divito EB, Bondy JI, DiPerna ZJ … +2 more , Fochtman FW, Divito CB
J Anal Toxicol · 2025 May · PMID 40036597 · Publisher ↗
Peripheral blood is considered the gold standard for postmortem toxicological analysis. However, vitreous fluid (VIT) has been described as more resistant to postmortem redistribution and may act as an isolated matrix, p...
Peripheral blood is considered the gold standard for postmortem toxicological analysis. However, vitreous fluid (VIT) has been described as more resistant to postmortem redistribution and may act as an isolated matrix, preserving postmortem drug concentrations. To determine the utility of VIT analysis compared to traditional blood analysis for 6-acetylmorphine, morphine, cocaine, benzoylecgonine, fentanyl, and norfentanyl, paired peripheral blood and VIT were collected and analyzed in 122 postmortem cases from Western Pennsylvania. In this study, we tested the frequency of detection and performed analyses to correlate drug concentrations in both matrices. We demonstrate that VIT provides a viable matrix for the postmortem analysis of several drugs of abuse and their metabolites. However, when both matrices are available for analysis, VIT, when compared to whole blood, is not optimal for all analytes. These differences are likely due to differences in physiochemical properties and other pharmacokinetic parameters.
A fully validated LC-QTOF-MS screening workflow for the analysis of drugs in oral fluid.
Coulter C, Gonzales J, Coulter CA … +2 more , Wagner J, Moore C
J Anal Toxicol · 2025 Apr · PMID 39964060 · Publisher ↗
A simple liquid-liquid extraction procedure followed by liquid chromatography-quadrupole time of flight tandem mass spectrometry (LC-QTOF-MS) analysis for drugs in oral fluid collected with the Quantisal™ device has been...
A simple liquid-liquid extraction procedure followed by liquid chromatography-quadrupole time of flight tandem mass spectrometry (LC-QTOF-MS) analysis for drugs in oral fluid collected with the Quantisal™ device has been developed. The decision point cut-off concentrations were at or below those recommended by the National Safety Council's Alcohol, Drugs, and Impairment Division (NSC-ADID) for toxicological investigation of driving under the influence of drugs cases. Currently, the American Acadamy of Forensic Sciences and the Academy Standards Board (ANSI/ASB) Standard 120 does not cover the analysis of oral fluid collected in impaired driving investigations; instead guidance from the NSC-ADID was used. The supporting mass spectral-based screening library was adapted from commercially available databases and included Tier 1 and Tier 2 recommended compounds. Further, the additional inclusion of novel psychoactive substances and synthetic cannabinoids was based on the Center for Forensic Science Research and Education's quarterly publications of 2023. Metabolites from those publications were not included in this method since, with some exceptions, parent drugs are the dominant compounds in oral fluid. Briefly, Quantisal™ (1 mL) was mixed with organic solvents, centrifuged, and decanted; followed by a second liquid-liquid process which extracted all the drugs in a single aliquot. A gradient liquid chromatography program using 0.1% formic acid in water and 0.1% formic acid in methanol was used and the runtime was 10 minutes. LC-QTOF-MS settings were optimized to promote greater sensitivity for a wide range of drug classes. The method was fully validated using ANSI/ASB 036 Standard Practices for Method Validation in Forensic Toxicology as guidance. Interference studies, limit of detection, precision at and around the decision points, ionization suppression/enhancement, and processed sample stability up to 96 hours were completed for each drug in the library database. While ion suppression or enhancement of the analytes varied greatly, the decision point was not significantly affected and internal standards that mimicked similar responses were chosen for each analyte. The method was applied to proficiency program samples, routine samples received in the laboratory, and blind samples screened against the search engine. The optimization of specific tune characteristics and instrument settings allowed the user to meet or exceed recommended screening limits for drugs in Quantisal™ collected oral fluid samples without the need for immunoassay testing.
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