Search Results (166)

Despite their significance as forensic targets, alkyl nitrites, classified as illegal drugs, have received little attention in forensic analysis due to their high volatility and chemical instability. Here, we present a high-performance analytical approach using a pulsed dc soft plasma ionization-quadrupole mass spectrometry (pulsed dc SPI-MS) system, uniquely designed to operate using ambient air as the discharge gas. In this system, the modulation of the duty ratio functions as a “structural probe” to identify reactive isomers. Unlike conventional dielectric barrier discharge (DBD) sources that typically operate at atmospheric pressure, our SPI system utilizes a controlled pressure regime of several kPa, where the nitrogen in the ambient air effectively functions as a third-body gas to suppress excessive internal energy. The control of the duty ratio in our pulsed dc SPI source allowed for the successful manipulation of ion–molecule reaction pathways for highly reactive analytes. By optimizing several parameters, including duty ratio and discharge pressure, we achieved a unique ionization regime where the molecular-related ion [2 M − 3 H]⁺ was predominantly detected as the base peak with minimal fragmentation. Notably, by reducing the duty ratio from 50% to 5%, both the target ion occupancy and signal intensity were significantly enhanced, achieving a limit of detection (LOD) as low as 0.16 parts per million by volume (ppmv). This sensitivity is several orders of magnitude higher than previously reported thresholds, enabling rapid identification of C4–C6 alkyl nitrite isomers. This method transforms the duty ratio into a powerful diagnostic tool for identifying reactive intermediates, providing a practical and efficient approach for the onsite identification of illegal alkyl nitrites in forensic and security fields. Full article

Fentanyl is a potent analgesic widely used in clinical practice. Fentanyl and its analogues are seriously abused and are emerging in the illegal drug market, leading to numerous intoxication cases. However, assessment of the potency of the pharmacological effect of these novel fentanyl analogues remains limited and inconsistent across studies. The development of novel analgesics has largely relied on the assessment of mu opioid receptor (MOR) binding affinity, with insufficient verification through the assessment of antinociceptive effects. This study evaluated the antinociceptive effects of 25 fentanyl analogues to investigate the relationship between chemical structure and antinociceptive effect. In this study, hot plate tests were conducted in mice to generate time–effect and dose–effect curves for the evaluation of the antinociceptive effect of fentanyl and its analogues. The results demonstrated that the antinociceptive effects of fentanyl analogues were dose- and time-dependent. The potency of the antinociceptive effect observed in this study generally aligned with the corresponding MOR binding affinities reported in the literature, although several analogues exhibited discrepancies. Structural modifications in different regions of the fentanyl scaffold affect the antinociceptive potency to different degrees, and the duration of action also varied across fentanyl analogues. Furthermore, opioid-induced hyperalgesia (OIH) was observed following administration of several fentanyl analogues, raising potential concerns regarding their abuse liability and development for analgesic purposes. Taken together, this study systematically evaluated and compared the antinociceptive effects of fentanyl analogues. The findings clarify the relationship between chemical structure and the antinociceptive effect, providing valuable insights for drug regulation and the development of novel analgesics. Full article

Cannabis is the most-used psychoactive drug in Aotearoa—New Zealand (NZ); recreational use remains illegal, while medicinal use was legalized in 2020. Cannabis use is associated with increased risk of injury; however, there is little known on the causes and circumstances of cannabis-related fatal injuries. This retrospective population study utilized coronial case files to describe the contribution and circumstances of cannabis-related fatal injuries in NZ. Between 2012 and 2016, cannabis was reported in 273 of 3599 unintentional/assault injury deaths (1.32 deaths per 100,000 person-years, 95% CI 1.17, 1.49). High-risk groups included males aged 15–44 years, Indigenous Māori, and those in deprived areas, for whom higher rates of post mortem testing were conducted. Cannabis-related fatalities mainly resulted from road crashes and multi-drug poisonings with concomitant alcohol use common, especially in traffic crashes on public roads (49% of concomitant use). Cannabis use was mainly observed in the decedent (n = 256, 94%). One in five deaths involved a worker, either as a user or as a bystander to another’s use. Coronial files identified important opportunities for safety countermeasures targeting cannabis use among drivers and its concomitant use with alcohol. Improved coverage of post mortem testing could address data limitations, including biased testing patterns and missing medical use. Full article

Microfluidic paper-based analytical devices (µPADs) convert ordinary cellulose into an active analytical platform where capillary gradients shape transport, surface chemistry guides recognition, and embedded electrodes or optical probes translate biochemical events into readable signals. Progress in fabrication—from wax and stencil barriers to laser-defined grooves, inkjet-printed conductive lattices, and 3D-structured multilayers—has expanded reaction capacity while preserving portability. Detection strategies span colorimetric fields that respond within porous fibers, fluorescence and ratiometric architectures tuned for low abundance biomarkers, and electrochemical interfaces resilient to turbidity, salinity, and biological noise. Applications now include diagnosing human body fluids, checking food safety, monitoring the environment, and testing for pesticides and illegal drugs, often in places with limited resources. Researchers are now using learning algorithms to read minute gradients or currents imperceptible to the human eye, effectively enhancing and assisting the measurement process. This perspective article focuses on the newest advancements in the design, fabrication, material selection, testing methods, and applications of µPADs, and it explains how they work, where they can be used, and what their future might hold. Full article

A total of 250 known and novel compounds—ketamine and serotonergic psychedelics or their analogues—designed to target depression, addictions and/or other mental or neurological disorders and developed as “recreational” (illegal) drugs from three chemical families, ergolines, tryptamines and phenylethylamines, were investigated in the context of their ability to cross the human placenta. Using a novel multivariate model involving compounds’ drug-likeness (according to Lipinski’s Ro5), caco-2 membrane permeability, fraction unbound to plasma proteins, steady-state volume of distribution and the total count of heteroatoms (non-carbon atoms with hydrogens included), it was established that the majority of studied compounds are likely to cross the placenta easily, most probably by the passive diffusion mechanism. Atomic contributions of structural elements of studied compounds were investigated using the Morgan fingerprinting algorithm and it was postulated that the fragments promoting transport of compounds across the placenta are carbonyl, hydroxyl, nitro- and phosphoryloxy groups—rigid polycyclic structures, bulky alkyl/aryl groups and halogen atoms restrict the trans-placental passage. All studied compounds are expected to be relatively easily obtained by synthetic routes, which makes them an interesting target for manufacturers of illegal drugs and warrants the need to pursue pharmacological studies of these compounds in silico. Full article

Background: Adolescents face unique challenges as they transition from childhood to adulthood, which can be marked by risky behaviours such as substance use and sexual activities. The present study analyses the relationship between risky sexual behaviour and the use of psychoactive substances, namely alcohol, cannabis, and other illegal substances, among students aged 15–16 years in 23 European countries, to investigate potential between-country differences. Method: Data were extracted from the 2019 European School Survey Project on Alcohol and Other Drugs (ESPAD) cross-sectional survey. Risky sexual behaviour was defined as self-reported unprotected sex. Substance use, other individual risk behaviours, and parenting indicators were investigated as key predictors. Results: A 9.8% of 16-year-old students in Europe reported sexual intercourse without a condom in the past year, and 7.8% had unprotected sex while not using alcohol/drugs, with a higher prevalence observed among males (8.5%) than among females (7.1%). Prevalence ranged from 3.2% in Georgia to 16.0% in Sweden. The multivariate analysis revealed significantly higher odds of engaging in sexual intercourse without a condom in illicit drug users (cannabis, inhalants, cocaine, ecstasy) and heavy episodic drinkers, students who went out in the evening, and those belonging to non-traditional families. Conclusions: Unprotected sex in the past year and substance use are strongly associated amid 16-year-old students in Europe. The prevalence of risky sexual behaviours across European countries does not follow a clear geographical pattern, suggesting that simple macro-level factors, such as broad regional or cultural groupings, may only partially explain prevalence differences. Full article

Background/Objectives: Thyroid hormones, considered safe in therapeutic doses, are used to treat hypothyroidism, a common condition. Due to a combination of factors, including their mechanism of action, availability, and low price, these drugs are used illegally, mainly to improve performance, to assist in weight loss, or for attempting suicide. Their overuse can lead to serious health consequences, including death. Although thyroid hormones are abused, there are no studies assessing the scale, characteristics, and consequences of their illegal use. The aim of this study was to evaluate case reports of thyroid hormone poisoning from the last 30 years, assessing their dynamics and characteristics. Methods: Full-text clinical case studies were obtained by searching PubMed, Google Scholar, MEDLINE, Embase, Web of Science, and Scopus for the following terms: “thyroid hormones”, “thyroxine”, “levothyroxine”, “triiodothyronine”, and “liothyronine”, as well as “intoxication”, “overdose”, and “poisoning”. This study adhered to Preferred Reporting for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews. Results: Thyroid hormones are abused particularly by athletes, persons trying to lose weight, or those attempting suicide. There has been an upward trend in thyroid hormone poisoning over the past 30 years, particularly since 2015. The same trend has been observed in cases of thyroid hormone use for doping, among other performance-enhancing drugs. Thyroid hormone use for doping was the most common cause of poisoning with these drugs, with other clinical manifestations from poisonings due to other causes. No upward trend has been observed in the use of thyroid hormones in suicide attempts since 2017, as this number remains stable. Conclusions: Although exploratory in nature, our work indicates that thyroid hormone poisoning, associated mostly with the illegal use of anabolic–androgenic steroids, exhibits an increasing tendency. Moreover, thyroid hormone abuse is an important issue in suicidology. Full article

Health wines are alcoholic beverages produced by infusing traditional liquors or rice wines with natural, medicinal, and food-safe ingredients. However, to accelerate efficacy, some manufacturers illegally adulterate health wines with phosphodiesterase type 5 (PDE-5) inhibitors, which may cause severe adverse effects. This study developed a method based on ultra-high-performance liquid chromatography–time-of-flight mass spectrometry (UPLC–TOF/MS) for the rapid screening and identification of 68 PDE-5 inhibitors illegally added to health wines. After optimizing the sample preparation procedure, chromatographic conditions, mass spectrometric parameters, and primary and secondary mass spectra of the 68 PDE-5 inhibitors were acquired as reference standards. Retention times and mass spectral data were imported into the Personal Compound Database and Library, establishing a high-resolution screening database with matched drug names, molecular formulas, and accurate molecular weights. A quantitative method was validated using 11 commonly adulterated compounds, including sildenafil. The response was highly linear (r ≥ 0.9988; 0.8–400 μg/L) with low detection limits (0.2–1.0 μg/L). The average spiked recoveries were 71.2–104.1%, with relative standard deviations of ≤10.1%. Among 59 commercial health wine samples, three batches tested positive for PDE-5 inhibitors (detection rate: 5.1%). The proposed method can assist market surveillance even when reference standards are unavailable for all compounds. Full article

In Hungary, the consumption of any alcoholic beverage before driving is illegal. A person is considered drunk if they have a blood alcohol concentration of 0.5 g per liter or more. The situation regarding drug use is also disappointing. This research analyses these effects on transport and their “outcome” by evaluating analyses based on police data, driver training data, and experimental data. The research aims to further raise awareness of the public health importance of this problem through a case–control study. Descriptive and correlational, statistical calculations were performed with a significance value of p < 0.05. Between 2019 and 2023, there were 10–13.000 drunk driving offenses and 1.000–1.300 drunk-driving accidents on the roads each year, most of which occurred in the capital and caused minor injuries. The results will be used to discover synergies to improve road safety. Full article

In this article, we propose a variant Poisson item count technique (VPICT) that explicitly accounts for respondent non-compliance in surveys involving sensitive questions. Unlike the existing Poisson item count technique (PICT), the proposed VPICT (i) replaces the sensitive item with a triangular model that combines the sensitive and an additional non-sensitive item; (ii) utilizes data from both control and treatment groups to estimate the prevalence of the sensitive characteristic, thereby improving the accuracy and efficiency of parameter estimation; and (iii) limits the occurrence of the floor effect to cases where the respondent neither possesses the sensitive characteristic nor meets the non-sensitive condition, thus protecting a subset of respondents from privacy breaches. The method introduces a mechanism to estimate the rate of non-compliance alongside the sensitive trait, enhancing overall estimation reliability. We present the complete methodological framework, including survey design, parameter estimation via the EM algorithm, and hypothesis testing procedures. Extensive simulation studies are conducted to evaluate performance under various settings. The practical utility of the proposed approach is demonstrated through an application to real-world survey data on illegal drug use among high school students. Full article

Public health concerns related to food contaminants, including biotoxins, pesticide and veterinary drug residues, illegal additives, foodborne pathogens, and heavy metals, have garnered significant public attention in recent years. Consequently, there is an urgent need to develop rapid and accurate technologies to detect these harmful substances. Surface-enhanced Raman spectroscopy (SERS), due to its characteristics of high sensitivity and specificity enabling the detection of food contaminants within complex matrices, has attracted widespread interest. This review focuses on the application of noble metal-based nanocomposites as SERS-active substrates for food contaminant detection. It particularly highlights the structure–performance relationships of metallic nanomaterials, including gold and silver nanoparticles (e.g., nanospheres, nanostars, nanorods), bimetallic structures (e.g., Au@Ag core–shell), as well as metal–nonmetal composite nanomaterials such as semiconductor-based, carbon-based, and porous framework-based materials. All of which play a crucial role in achieving effective Raman signal enhancement. Furthermore, the significant applications in detecting various contaminants and distinct advantages in terms of the sensitivity and selectivity of noble metal-based nanomaterials are also discussed. Finally, this review addresses current challenges associated with SERS technology based on noble metal-based nanomaterials and proposes corresponding strategies alongside future perspectives. Full article

Agarwood, valued for its resin, has long been used in perfumery, incense, and traditional medicine. Its resin is primarily derived from species of Aquilaria and is produced through a still-unknown process in response to biotic or abiotic stress. Concerns regarding agarwood’s sustainability and conservation have emerged because of the substantial loss of natural resources due to overharvesting and illegal trade. To address these concerns, artificial techniques are being used to produce agarwood. The mechanism underlying agarwood production must be elucidated to enhance yield. The authentication of agarwood species is challenging because of morphological similarities between pure and hybrid Aquilaria species. Techniques such as DNA barcoding, molecular marker assessment, and metabolomics can ensure accurate identification, facilitating conservation. Artificial intelligence and machine learning can support this process by enabling rapid, automated identification on the basis of genetic and phytochemical data. Advances in resin induction methods (e.g., fungal inoculation) and chemical induction treatments are improving yield and quality. Endophytic fungi and bacteria promote resin production at minimal harm to the tree. Agarwood’s pharmacological potential—antimicrobial, anti-inflammatory, and anticancer effects—has driven research into bioactive compounds such as sesquiterpenes and flavonoids for the development of novel drugs. This systematic review synthesized current evidence on species authentication, induction techniques, and pharmacological properties. The findings may guide future research aimed at ensuring sustainable use and enhancing the medicinal value of agarwood. Full article

Xylazine (XYL), an FDA-approved veterinary tranquilizer, is being abused both as an opioid adulterant in a street-drug known as “Tranq-dope” and as a date rape drug. Given its now nearly ubiquitous use with fentanyl and fentanyl derivatives across the globe, XYL has become a primary target for researchers seeking to develop portable and cost-effective sensors for its detection. Electrochemical sensors based on the oxidation of XYL, while useful, have limitations due to certain interferents and inherent electrode fouling that render the approach less reliable, especially in certain sample matrices. In this work, modified electrode platforms incorporating layers of multi-walled carbon nanotubes for sensitivity along with semi-permeable polyurethane (PU) layers and host–guest chemistry using β-cyclodextrin for selectivity are deployed for XYL detection using complementary adsorptive cathodic stripping analysis. The modified electrode sensors are optimized to minimize high potentials and maintain fouling resistant capabilities and investigated to better understand the function of the PU layer. The use of adsorptive cathodic stripping differential pulse voltammetry indirectly indicates the presence and concentration of XYL within complex sample media (beverages and synthetic urine). When used in this manner, the modified electrodes exhibited an overall average sensitivity of ~35 (±9) nA/μM toward XYL with a limit of quantification of <10 ppm, while also offering adaptability for the analysis of XYL in different types of samples. By expanding the capability of these XYL sensors, this study represents another facet of tool development for use by medical professionals, first-responders, forensic investigators, and drug-users to limit exposure and help stem the dangerous and illegal use of XYL. Full article

Background/Objectives: Drug products on the pharmaceutical market must meet a number of requirements that guarantee their quality, safety, and efficacy. Accordingly, periodic inspection of the content of active pharmaceutical ingredients (APIs) in marketed drug products is carried out, confirming that they meet all quality and quantity requirements for a given drug formulation before the expiration date. Therefore, the purpose of this study was to evaluate the suitability of the most commonly used thermal analysis methods, differential thermal analysis (DTA), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), in the control of the composition of commercially available drug products. Results: Based on a review of the literature, it was shown that thermal methods can be useful in distinguishing drug products from different manufacturers, which guarantees their usefulness in quality control of finished drug products and detecting drug products from illegal manufacturers. They are also useful as tools for confirming the presence of APIs in dosage forms under investigation. The cited literature also indicates that DSC and TGA methods can be used in the quantification of APIs in marketed drug products and to detect non-compliant drug products. The use of chemometric techniques to interpret thermal data can eliminate the adverse effects of excipients on quantification results. Conclusions: Thermal methods are a good complement to chromatographic and spectroscopic methods, with the particular advantages of not needing any sample pretreatment, low sample weight, and short analysis time. Full article

In recent years, an increasing number of case reports have mentioned the presence of illicit nootropics, smart drugs or mind doping products on the market. To better understand the extent of the problem, a market surveillance study was organised by the General European Official Medicines Control Laboratory Network and associated member Australia to detect substandard, falsified or illegal medicines or dietary supplements containing unauthorised nootropic molecules of natural or synthetic origin. From January 2020 to September 2024, 159 different samples were documented, which yielded a comprehensive dataset of 166 molecular identification entries. Within this dataset, 34 distinct molecules were identified. Most samples were sold or presented as dietary supplements (49%) or medicines (32%). The vast majority (69%) were collected from the illegal market. Prescription drugs and non-authorised drugs only available on prescription in Russia were found in pharmacological quantities; some of the latter (noopept, phenylpiracetam and phenibut) were intercepted as large bulk quantities of raw material. Unauthorised novel foods, prescription or higher amounts of melatonin, and clinically uncharacterised research molecules were also reported. This study highlights the need for more active monitoring and screening of such products, as consumption of some of the reported samples could have detrimental health effects. Furthermore, as a large number of the samples were presented as dietary supplements, consumers may not be aware of the possible dangers and side-effects of these products. Full article