Journal of analytical toxicology最新文献

On-site drug screening of oral fluid samples has gained attention because of its convenience and rapid results. The aim of this investigation was to compare the results of preliminary screening for drugs in oral fluid samples collected from suspected drug-impaired drivers using DrugWipe 6S and WipeAlyser reader with the results obtained from blood samples. Additionally, we compared the DrugWipe test results with findings of drug traces detected within the used DrugWipe devices. Police officers selected a sample of 355 suspected drug-impaired drivers in 2023. They used DrugWipe 6S for preliminary drug screening of drivers. After the field drug testing of oral fluid, the apprehended drivers were brought to a physician for the collection of blood samples. The collected samples (DrugWipe devices and blood samples) were submitted to the Norwegian National Forensic Toxicology Laboratory for analysis. The proportion of positive DrugWipe results that were unconfirmed when analysing blood samples was 82% for opiates, 75% for cocaine, and ∼19%-20% for amphetamines, cannabis, and benzodiazepines. The proportion of negative DrugWipe results that were found positive in blood samples was for cannabis and benzodiazepines ∼13%-14%, and for other drugs <3%. Detected drug traces in the used DrugWipe devices corresponded well with DrugWipe readouts for cannabis, amphetamines, and cocaine. The lack of correspondence between DrugWipe test results for cocaine and findings in blood may be due to the fact that the concentration of cocaine in saliva is often much higher than in blood, and the DrugWipe test is very sensitive. In addition, degradation and elimination of cocaine before the blood sample is taken may contribute to cocaine concentrations below the cut-off concentration in blood. For opiates and benzodiazepines, traces of drugs were found in relatively few DrugWipe devices. Many unconfirmed positives for opiates were most likely due to cross-reaction with substances in 'snus' (snuff tobacco).

Δ9-Tetrahydrocannabinol (Δ9-THC) is the most prominent and main psychoactive cannabinoid found in cannabis. In forensic matters involving cannabis, such as drugged driving or workplace accident investigations, blood Δ9-THC determination is typically required. Venipuncture by a phlebotomist at a medical facility is often the standard blood collection protocol, but this procedure is time consuming and requires specialized training. Capillary blood collection at the site of a transportation or workplace mishap may provide a collection method that is logistically easier and may better reflect blood cannabinoid concentrations at the time of an incident. This study represents the first temporal comparison of the concentration of Δ9-THC and its primary metabolites in venous and capillary blood obtained from users following ad libitum inhalation of contemporary high-concentration cannabis products. Participants provided their own cannabis from a licensed Colorado dispensary and were instructed to smoke or vape ad libitum the amount most used for the desired effect during a 15-minute period. Capillary blood samples collected at the lateral shoulder using the TAP® II microneedle device and standard venipuncture samples at the forearm were collected contemporaneously at baseline and then 10, 30, 60, 90, and 140 minutes after the last inhalation and were analyzed for Δ9-THC, 11-hydroxy-Δ9-THC, and 11-carboxy-Δ9-THC by liquid chromatography-tandem mass spectrometry. Within-subject Δ9-THC concentrations trended lower, often up to 30 to 40%, in contemporaneous capillary blood samples than in venous blood samples until 140 min after cannabis smoking. Concentrations of the Δ9-THC metabolites 11-hydroxy-Δ9-THC and 11-carboxy-Δ9-THC were equivalent at all but the first timepoint after smoking. Due to logistical advantages, capillary blood collection by microneedle devices may be a viable option for qualitative detection of Δ9-THC and its metabolites soon after an incident or a quantitative determination if the samples are collected at least 2 hours after cannabis inhalation.

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.

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.

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.

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.

Amatoxin-containing mushrooms, which contribute to many intoxications each year, are of particular interest for clinicians and toxicologists, as patients require special treatment in hospitals. 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 and expensive equipment are required. Therefore, a lateral flow immunoassay (LFIA) for the 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.

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.

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.