Journal of analytical toxicology最新文献

This study evaluated the performance of the Immunalysis Tapentadol 343 Urine Enzyme Immunoassay (EIA) screening kit, focusing on the prevalence of false-positive results due to cross-reactivity with tramadol. Tapentadol is a dual-action analgesic, modulating μ-opioid receptors and inhibiting norepinephrine reuptake, while tramadol, a structurally related compound, is a weak μ-opioid receptor agonist and norepinephrine/serotonin reuptake inhibitor. Cross-reactivity between these compounds can complicate urine drug screening results for adherence monitoring in chronic pain management. A total of 28 samples initially produced false-positive results for tapentadol BNl using the Immunalysis Tapentadol 343 Urine EIA screening kit. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to confirm the absence of tapentadol. Of the false-positive samples, 61% contained tramadol at concentrations below the manufacturer-reported cross-reactivity threshold of 60 000 ng/mL, indicating assay limitations in specificity. To address this issue, a newly reformulated Immunalysis Tapentadol 343UR Urine HEIA kit was evaluated for tramadol cross-reactivity. Upon retesting the 28 false-positive samples with the reformulated kit, no false positives were detected, with results consistent with LC-MS/MS confirmation. The rate of false-positive tapentadol screens in urine has substantially reduced since the implementation of the new tapentadol kit in routine testing. These findings demonstrate the importance of assay verification to assess cross-reactivity, particularly for structurally related compounds. The reformulated Immunalysis Tapentadol 343UR kit shows improved specificity, reducing false-positive rates and enhancing the accuracy of tapentadol detection in clinical and forensic toxicology applications.

Hair analysis is a valuable tool in forensic toxicology, providing extended detection windows and critical insights into drug testing, usage trends, and drug-facilitated crimes. This systematic review was conducted using Scopus, Web of Science, and PubMed databases from March 2017 to September 2024, and evaluated 19 studies (16 research articles and 3 case reports) on the detection of γ-hydroxybutyrate (GHB) in hair. This review examines recent studies on GHB concentrations in hair, focusing on both endogenous and exogenous concentrations resulting from illicit and prescribed use, as well as the analytical methods employed. This review includes decontamination parameters, extraction techniques, and sample sizes used during the analytical method. New studies report that endogenous GHB levels range from 0.2 to 5.5 ng/mg, while exogenous levels vary widely from 0.3 to 239.6 ng/mg. Additionally, published results indicate that the frequency of use may be more significant than the dosage for exogenous GHB to be incorporated into the hair. A novel adjacent segmentation method has been proposed to differentiate endogenous from exogenous GHB, identifying local peaks within adjacent hair segments. Research into GHB-glucuronide as a biomarker has found it unreliable due to inconsistent correlations with exogenous use. Further research is needed to refine the interpretation of GHB levels in forensic applications.

N, N-Dimethyltryptamine (DMT) is a hallucinogen found in the South American Psychotria viridis plant and is the major psychoactive ingredient in the brew ayahuasca. In this report, we performed a review of the surrounding literature and detail two deaths which recently occurred in the UK following DMT use. A literature search of both academic (PubMed, GoogleScholar) and media (using Google search engine) publications was performed to identify previously reported fatalities following DMT use. The National Programme on Substance Use Mortality (NPSUM) was also searched for deaths which have occurred in the UK following DMT use. Literature search-There have been three previous reports of fatalities following DMT use, all deemed accidental in nature, with DMT consumption taking place as part of an ayahuasca ceremony in two of these cases. NPSUM cases-Two cases were identified (Case Report 1 [CR1] & Case Report 2 [CR2]), neither of which occurred in the context of an ayahuasca ceremony. DMT was detected and quantified in femoral blood in both cases (CR1 0.23 mg/l; CR2 0.24 mg/l). There was evidence of polydrug use in both cases (CR1 n = 6; CR2 n = 9), which in each case included additional compounds which can increase serotonergic drive (CR1 cocaine, amphetamine; CR2 venlafaxine, mirtazapine). There have been two recent deaths following DMT use in the UK, both in the context of polydrug use which may have caused death due to excessive serotonergic innervation leading to serotonin syndrome. Polydrug use is increasingly common in the UK, and users of unregulated drugs should caution their use in combination with other unregulated drugs and also any prescribed medications.

Transdermal drug delivery has been of particular interest to pharmaceutical research for decades, but is also becoming increasingly relevant in the field of sports drug testing. As shown in the past, the (unintentional) oral ingestion of trace amounts of prohibited selective androgen receptor modulators (SARMs), e.g. due to product contamination, can lead to an adverse analytical finding (AAF) in doping controls. Another site of exposure is presented by the skin, as it provides a large surface for drug penetration. However, the extent of diffusion through various layers of the skin and into the blood vessels depends, among other things, on the physicochemical and biological properties of a substance. The objective of this project was to simulate a transdermal contamination scenario and investigate the skin penetration and subsequent metabolism of microdoses of three commonly used SARMs: LGD-4033, RAD140, and S-23. For this purpose, an administration study was conducted, in which either 10 or 50 µg of the substances were applied to the lower forearm of 5 volunteers each. The collected urine samples were analyzed via LC-MS/MS following enzymatic hydrolysis and solid-phase extraction. This methodical approach is distinguished by its high sensitivity, enabling the detection of at least 5 pg/mL for LGD-4033 and S-23. After 10 µg administration, LGD-4033 and S-23 as well as associated metabolites were detected, while RAD140 was only detected in urine samples of one subject (n = 5). Following the application of 50 µg, RAD140 was detected in all subjects (n = 5) for up to 9 days, and additional metabolites of LGD-4033 and S-23 were identified. The long-term metabolite of LGD-4033 (M5b) was detected up to 12 days after the dermal administration of 10 µg, and up to 25 days after application of 50 µg, while S-23 was traceable for up to 16, respectively 24 days. It was demonstrated for all three SARMs that they penetrate the skin and may-even in trace amounts-produce AAFs when administered transdermally. Information on urinary concentrations and metabolism following transdermal administration of SARMs may assist in the interpretation of AAFs, particularly when dermal contamination or intentional doping via the skin is discussed.

Postmortem vitreous humor may be used for toxicological analysis if blood and urine are unavailable or where postmortem blood is thought to be affected by postmortem changes. Use of vitreous humor has been restricted by the available sample volume and instrument sensitivity. However, the advent of combined screening and quantitative methodologies using liquid chromatography-high-resolution mass spectrometry makes analysis of vitreous humor possible. This study examines an existing combined screening and quantitative methodology to determine if it is suitable for use with vitreous humor. Analysis of standard solutions containing 48 compounds showed % difference between expected and measured values in the range -15.59 to 20.81, -15.73 to 18.34, -14.32 to 19.77, and -19.90 to 19.78 for very low, low, mid and high range standard solutions respectively. Intraassay %CV was in the range 0.93 to 10.10, 1.35 to 15.19, 3.07 to 11.56, and 2.04 to 8.29 and interassay %CV was 0.96 to 17.40, 3.68 to 17.03, 3.94 to 17.12, and 4.87 to 16.55. Limits of quantitation range from 0.002 to 0.5 and limits of detection from 0.0008 to 0.06 mg/L. There was no significant interference from ion suppression or isobaric compounds and very little carryover. Dilution 1:2, 1:5 and 1:10 with vitreous humor gave acceptable results. Comparison of screening results from 129 postmortem cases showed that most compounds detected in blood and/or urine were also detected in vitreous humor. Compounds more readily detected in vitreous humor included 6-monoacetylmorphine, cocaine, codeine, dihydrocodeine, olanzapine, desmethylzopiclone, diazepam, cocaethylene, and desmethylmirtazapine. Compounds more readily identified in blood and/or urine included desmethylsertraline, EDDP, nordiazepam, papaverine, paracetamol, and morphine. The assay is suitable for screening and quantitation of drugs and their metabolites in vitreous humor and can be used where blood and urine are unavailable, or where the analysis of vitreous humor may provide useful information.

Drug overdoses are among the most common causes of death in the United States, with synthetic opioids such as fentanyl implicated in the majority of overdose fatalities in the last 10 years. As such, effective rapid assays capable of screening against large drugs of abuse panels that include synthetic opioids are critical tools for detecting drug abuse. The iScreen™ Urine Test FUO Drug Screen Cup (Abbott Laboratories) is a multiplexed lateral flow device designed for the preliminary qualitative screening drugs of abuse in urine for forensic applications, and can be used to simultaneously screen urine specimens for up to 17 different drugs of abuse, with multiple potential configurations of assays and cutoffs to support 22 different assay/cutoff combinations. This investigation focused on evaluating the performance of the iScreen™ Urine Test FUO Drug Screen Cup for analytical sensitivity, cross-reactivity characteristics for structurally-related compounds, and method comparison versus the gold standard method (GC-MS or LC-MS/MS). Analytical sensitivity testing demonstrated ≥95% accuracy for all 22 assays during evaluation against both negative and 3x cutoff positive control specimens, and all 22 assays achieved ≥89% concordance with the established reference methodologies in testing with positive and negative human urine specimens.

Background: Nitazenes are a class of new psychoactive substances (NPS) belonging to the synthetic opioids. It has potent μ- opioid receptor agonist activity.In this study, we investigated an authentic forensic human blood and urine sample from an individual that died from the use of N, N-dimethyl etonitazene.

Objective: To enable rapid analysis in authentic forensic sample, a method was developed utilizing in silico metabolite prediction and liquid chromatography high-resolution mass spectrometry (LC-HRMS) for blood and urine samples.

Method: In this study, LC-HRMS was used to analyse authentic blood and urine samples, and Sygma software was used to predict metabolites. Based on the predicted results, targeted analysis methods of LC-HRMS data were used to study the metabolites of blood and urine.

Result: N, N-dimethyl etonitazene and 7 metabolites were identified in blood and urine samples. Among them, there were four phase I metabolites, which respectively correspond to four metabolic pathways :N-demethylation (M1), 5-amination (M2), 4'-hydroxylation (M4), N-oxidation(M6). There were three phase II metabolites corresponding to two metabolic pathways respectively :acetylation (M3), glucuronidation (M5, M7). M1, M2 and M3 were identified in blood sample, and all metabolites were identified in urine sample.

Conclusion: In this study, Sygma software was used to predict metabolites, and LC-HRMS method was employed to specifically analyse the metabolites of N, N-dimethyl etonitazene in authentic forensic human samples. The time required for data analysis was significantly reduced through in silico metabolite prediction. We recommend the 5-amination metabolite (M2) as a potential biomarker in blood and urine samples of N, N-dimethyl etonitazene. In addition, this study filled the gap in the study of N, N-dimethyl etonitazene metabolism. It also provided real data supplementation for the metabolism of nitazene analogues. The prediction of metabolites by using Sygma provided a certain reference for the future application of artificial intelligence in the field of forensic analysis.

Herein we report the confirmation of N-debenzisothiazole-lurasidone as a lurasidone degradation product associated with postmortem toxicology casework. Confirmation was realized by unambiguous synthesis and comparison of its LC-MS/MS properties to the lurasidone degradation product in postmortem blood using liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). The mechanism of formation of this degradant in blood is proposed to be primarily enzymatic, given it has only been previously presumptively reported in one in vitro stability study following oxidative stress conditions. It has not been reported in other in vivo pharmacokinetic and in vitro stability studies assessing lurasidone stability toward acid, alkali, oxidation, photolysis, and heat. The detection of N-debenzisothiazole-lurasidone in postmortem casework indicates that, where possible, it should be included in toxicology screening methods targeting psychoactive compounds. Until such time that a commercially available reference standard of N-debenzisothiazole-lurasidone is available, the comprehensive accurate mass and mass spectral data of N-debenzisothiazole-lurasidone that are now available enable its inclusion as a "suspect target" in high-resolution-mass-spectrometry screening methods.