Drug Testing and Analysis最新文献

The increasing misuse of opioids in Europe is an alarming trend, leading to severe social and health consequences. Heroin, a highly potent and addictive opioid, remains the main contributor to the health burden associated with opioid use in the region. Illicit drug characterization and profiling offer valuable insights into the complexity of heroin seizures, assisting law enforcement agencies and forensic experts in gathering evidence for legal proceedings. This study provides a comprehensive overview of the composition of heroin seizures and assesses the feasibility of an electrochemical fingerprint approach for the detection of heroin and its associated components. In the initial phase, the primary focus was on developing an electrochemical sensor optimized for heroin detection. The sensor's performance was validated using street samples provided by Sciensano, a Belgian health institute, ensuring its accuracy and reliability in identifying heroin. Once the capabilities of the sensor were demonstrated, the discrimination of alkaloids and cutting agents in seized samples was integrated into a customized software script. Subsequently, an extensive validation process was conducted using a new dataset of heroin seizures from the Belgian National Institute for Criminalistics and Criminology. The follow-up verification confirmed the sensor's effectiveness in detecting heroin, cutting agents, and alkaloids, highlighting its potential as a valuable tool for drug profiling. This portable, user-friendly device with automatic readout could become essential for forensic experts, law enforcement, and harm reduction efforts in addressing the opioid crisis.

In recent years, a scenario involving milk contamination by biotransformation products of the veterinary drug Emidonol has received widespread publicity. Emidonol is intended for use in cattle under pathological conditions accompanied by hypoxia. The drug dissociates into two antihypoxants-meldonium, a metabolic modulator prohibited in sports, and emoxypine, which also has antioxidant properties. A small-scale pilot study involved three volunteers consuming a single 900-mL dose of unpasteurized cow's milk collected on the last (15th) day of treatment with the drug. The mean estimated urinary concentration of emoxypine peaked between 7- and 8.5-h postadministration (1360 ± 240 ng/mL), elimination time being approximately 50-54 h. The mean estimated urinary concentration of meldonium peaked between 5.8- and 9.0-h postadministration and was 322 ± 68 ng/mL, elimination time being approximately 35-45 h. The simultaneous presence of emoxypine and meldonium in urine samples may be indicative of the consumption of Emidonol-contaminated milk, which may facilitate the identification of cases of unintended doping in sport.

Distinguishing between intake of the prohibited substance trimetazidine from administration of approved migraine medicine containing the nonprohibited substance, lomerizine, is crucial for anti-doping control laboratories. Investigations in males after lomerizine intake have been conducted leaving lomerizine M6 as the most useful metabolite. To our knowledge, the excretion profile of lomerizine among women has not been studied and leaves a potential gap to be misused by athletes in the case of appeal of a reported adverse analytical finding. We have investigated lomerizine M6 in women to address the gender-specific biology to correctly detect misusage of the prohibited substance trimetazidine within sports. To determine the importance of lomerizine M6 in trimetazidine cases, we analyzed urine samples collected from 12 individuals (eight females and four males) over 144 h, after oral intake of 5-mg lomerizine dihydrochloride. A dilute and shoot method was used, and the samples were analyzed on a LC-HRMS instrument. In all study subjects, trimetazidine was found from 2 h up to 48 h, and lomerizine M6 was detected from 2 h and onward. Lomerizine was only detected above the limit of identification of the method for a few of the subjects. The study demonstrated that by monitoring lomerizine M6, it was possible to determine the origin of trimetazidine in women. The metabolism for lomerizine dihydrochloride does not appear to differ significantly between genders. However, lomerizine M6 concentrations are not always higher than trimetazidine concentrations. Special care should be taken when interpreting trimetazidine concentrations at 1 ng/mL or below.

Over the past few years, dried blood spots (DBS) have been approved as a valid matrix for drug testing in sport. They undoubtedly offer advantages but also pose analytical challenges. For example, various DBS supports are nowadays available (polymeric and cellulose based) and an extraction method suitable for one support is not necessarily transferable to a different one. Herein, we present a qualitative screening method for the detection of a representative selection of small peptides and their metabolites in both cellulose and polymeric DBS. The analytes were extracted using an extraction solvent containing formic acid 1% in water/acetonitrile/methanol (70/15/15), followed by a second extraction with acetate buffer. To remove interferences and increase sensitivity, the combined extracts were further purified using solid-phase extraction (mixed-mode, weak cation exchange). Analysis was performed using ultrahigh-performance liquid chromatography combined with high-resolution mass spectrometry (orbitrap Q-Exactive). The analysis time was 7.5 min, and the acquisition was performed in full-scan mode, with the addition of some product ion scan acquisitions to increase selectivity or sensitivity for a few compounds that were particularly challenging. The method permits the analysis of small peptides on both polymeric and cellulose DBS samples with the same procedure for either matrix. Validation was performed following the World Anti-Doping Agency regulations, and the method proved satisfactory in terms of selectivity and sensitivity (limits of detection in the low ng/mL range) and applicable to the analysis of sport samples for the detection of small peptides.

A novel patent-based effervescent tablet was developed and evaluated as a selective filter for reducing hazardous chemical compounds in hookah smoke. The study combined gas chromatography-mass spectrometry (GC-MS) and atomic absorption spectroscopy (AAS) to identify and quantify major toxicants. Hookah smoke was trapped using cellulose nanofiber-based solvent chambers and latex puff chambers, followed by analysis of volatile organic compounds (nicotine, propylene oxide, formaldehyde, crotonaldehyde, acrolein, acetaldehyde, 1,3-butadiene, benzopyrene, pyridine, phenol, benzene) and potentially toxic trace elements (PTEs) such as lead, mercury, cadmium, and chromium. Detection limits (LODs) ranged from 0.003 to 0.04 mg/g, with relative standard deviations (RSDs) below 13%. The effervescent tablet reduced > 81% of hazardous compounds while selectively lowering nicotine and flavor by approximately 15%, maintaining user acceptability. Compared with cigarette smoke, unfiltered hookah smoke contained significantly higher levels of aldehydes and polycyclic aromatic hydrocarbons, whereas filtered hookah smoke showed markedly lower contaminant concentrations than both cigarette and e-cigarette smoke. The proposed method demonstrates innovation by integrating a user-friendly, selective effervescent tablet with high recovery (92%-102%) and accuracy, offering a practical strategy for harm reduction in hookah smoking.

This paper describes the detection and longitudinal monitoring of cyclosporine in plasma and urine after subconjunctival implant administration in a horse. Sensitive liquid chromatography tandem mass spectroscopy (LC-MS/MS) methods for detecting cyclosporine in horse plasma and urine have been developed and validated, with estimated limits of detection down to 1 pg/mL in both matrices. The developed methods enabled longitudinal monitoring of cyclosporine levels in blood and urine samples collected over 6 months from a horse that had received an ocular cyclosporine implant.

The presence of microplastics (MPs) in human tissues has raised growing concerns, necessitating robust protocols for their reliable extraction and analysis. This study systematically evaluated and optimized digestion protocols to efficiently process a variety of human tissues-placenta, lung, kidney, adipose tissue, muscle, spleen, liver, thyroid, and brain-while preserving the integrity of MP particles. Initial assessments employing single-reagent protocols such as nitric acid (HNO₃), proteinase K enzymatic digestion, and Fenton oxidative digestion demonstrated limited effectiveness, due to incomplete tissue breakdown or formation of turbid digestates that hindered filtration. Building upon these results, combined digestion approaches were investigated to improve organic matter removal and facilitate filtration through fine pore-size filters (0.2 μm). The optimized 3-day protocol included an initial oxidative Fenton digestion followed by enzymatic digestion (proteinase K). The final step involved lipid removal through ethanol addition and sonication, resulting in clear digestates amenable to filtration. This protocol efficiently digested complex tissue matrices, reducing filter clogging at 1-μm size pore and preserving various common MP polymers, including low-density polyethylene (LDPE), polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), and polyamides (PA6 and PA12). Application of the optimized digestion allowed successful isolation and characterization of MPs using optical microscopy and Raman spectroscopy. The method showed improved reproducibility and reliability over single-reagent protocols, making it suitable for comprehensive MP analysis in human tissues. The application of an efficient and robust protocol for tissue digestion may contribute to advance human exposure assessment and toxicological studies related to MP contamination.

Chronic exposure to pesticides can cause carcinogenic, reproductive, neurological, and endocrine-disrupting effects. Hair analysis is a valuable biomonitoring tool to assess human exposure to pesticides. We determined the presence of pesticides, their metabolites, and other environmental pollutants in the hair of children in an agricultural area of Paraguay. We analyzed 152 pesticides and environmental chemicals in hair samples from 51 children (2-14 years, mean ± SD = 8.5 ± 3.3 years) living in Colonia San Juan, a rural community in Paraguay. The locality is surrounded by soybean crops, and the community engages primarily in family farming. Eighty of the 152 compounds (52.6%) were detected. Each child's sample contained an average of 55 ± 3.7 compounds (range 48-65), including organophosphates, pyrethroids, neonicotinoids, fungicides, herbicides, and endocrine disruptors such as bisphenol A and bisphenol S. Thirty-seven compounds were present in all samples. Children in this rural community are simultaneously exposed to numerous pesticides and pollutants, highlighting the urgent need for stricter environmental protections and preventive health measures.

Already in the 1960s, the anabolic properties of Trestolone (7α-methyl-19-nortestosterone, MENT) were investigated in the context of cancer research, and MENT was found to be 10 times more potent regarding its anabolic properties compared to testosterone. The human metabolism of MENT was only investigated once in an antidoping context, and three urinary metabolites were identified, corroborating earlier findings from in vitro and animal experiments. Based on these metabolites, no doping control sample was reported to contain MENT or its metabolites in the last two decades albeit MENT is readily available via online distributors. One reason for the lack of adverse analytical findings in doping controls could be analytical challenges originating from the chromatographic properties of MENT and its urinary metabolites. Therefore, the human metabolism of MENT was reinvestigated employing an excretion study with deuterated MENT and metabolite detection based on hydrogen isotope ratio mass spectrometry in combination with high accuracy/high resolution mass spectrometry. Considering unconjugated, glucuronidated, and sulfated metabolites, 50 potential candidates were detected. In order to identify those metabolites suitable for sports drug testing, three volunteers administered a single oral dose of nondeuterated MENT, and all postadministration samples were investigated using triple quadrupole mass spectrometry-based determinations routinely employed in doping controls. From the 50 metabolites detected, two showed promising results with respect to their detection windows and suitability under routine measurement conditions. The specificity of the novel metabolites was ensured by the reanalysis of 200 routine doping control samples demonstrating the absence of potential coeluting compounds.

Synthetic cannabinoids (SCs) remain the most frequently detected class of new psychoactive substances (NPS) worldwide. Despite a recent decline in the overall number of newly reported NPS, SCs continue to emerge with remarkable structural diversity. Here, we report the discovery and structural elucidation of MDMB-5'Br-PINACA, a previously unreported SC identified in three seized herbal materials. The compound was isolated by semipreparative liquid chromatography and subsequently characterized using an integrated analytical approach combining gas chromatography-mass spectrometry (GC-MS), liquid chromatography-high-resolution mass spectrometry (LC-HRMS), and nuclear magnetic resonance (NMR) spectroscopy. In addition to MDMB-5'Br-PINACA, other SCs were detected in the analyzed materials, such as 5F-ADB and MDMB-4en-PINACA, also including the synthetic precursor MDMB-INACA. Other NPS classes were also observed, including designer benzodiazepines (N-desalkylgidazepam and bromazolam), and synthetic opioids (metonitazene). Recent years have also seen the emergence of brominated SCs as a strategy to evade legislative control, with several 5-bromo analogs detected across different regions. This analytical workflow enabled the unambiguous identification of MDMB-5'Br-PINACA and provided a detailed chemical profile of the seized samples, highlighting the continued evolution and complexity of NPS mixtures in herbal formulations. The findings emphasize the importance of continuous monitoring and early detection of emerging substances, which are essential not only for forensic and toxicological investigations but also for public health surveillance and the development of evidence-based drug control and harm-reduction policies.