María Ibáñez

The structural diversity and continuous emergence of synthetic cannabinoid receptor agonists (SCRAs) pose an important challenge to forensic and clinical toxicology. Understanding their metabolic pathways is essential for identifying reliable consumption biomarkers and improving toxicological screening strategies. This pilot study has investigated the influence of chemical structure on the metabolism of eight structurally diverse SCRAs: AMB-FUBINACA, ADB-FUBINACA, SDB-005, APINACA, CUMYL-4CN-BINACA, 5 F-AMB-PINACA, 5 F-AB-PINACA, and THJ-2201. The compounds were administered to male Sprague-Dawley rats from which serum and urine samples were analysed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Metabolite identification was achieved through different analytical strategies. Following structural elucidation, the in vivo metabolism for each SCRA was evaluated, and the corresponding metabolic pathways were proposed. A comparative analysis of the different metabolic reactions was subsequently performed, classifying biotransformations according to the site of occurrence within the molecule, to highlight both shared features and compound-specific pathways. The results demonstrated significant variability in the number and type of metabolites identified, underscoring the substantial influence of chemical structure on SCRA metabolism. Despite this variability, consistent biotransformations across compounds were also observed. Notably, this in vivo study allowed the detection of several metabolites not previously reported in in vitro models, demonstrating the added value of in vivo approaches in profiling the complete metabolic fate of SCRAs.

A comprehensive study assessed indoor air quality parameters, focusing on relevant air pollutants such as particulate matter (PM₁₀ and PM_2.5), gaseous compounds (CO, CO₂, formaldehyde, NO₂) and volatile/semi-volatile organic chemicals, as well as respiratory viruses (including SARS-CoV-2), fungi and bacteria in Spanish university classrooms. Non-target screening strategies evaluated the presence of organic pollutants inside and outside the classrooms. Saliva samples from teachers and students were collected to explore correlations between respiratory viruses in the air and biological samples. Indoor results revealed the punctual exceedance of recommended guidelines for CO₂, formaldehyde (HCHO), volatile organic compounds (TVOCs) and PM in the least naturally ventilated classrooms. Significant differences occurred between the classes, with the least ventilated one showing higher average concentrations of CO₂, HCHO, NO₂, PM₁₀ and PM_2.5. A respiratory virus (rhinovirus/enterovirus) was detected in the medium naturally ventilated classroom, although saliva samples tested negative. Suspect screening tentatively identified 65 substances indoors and over 200 outdoors, with approximately half reporting a high toxicological risk based on the Cramer rules. The study provides a comprehensive overview of indoor air quality, respiratory viruses and organic pollutants in university classrooms, highlighting the variations and potential health risks associated with ventilation differences.

A fast and automated strategy has been developed for identifying unknown substances in the atmosphere (concretely, in the particulate matter, PM₁₀) using LC-HRMS (MS³). A total of 15 samples were collected in three different areas (rural, urban and industrial). A sampling flow rate of 30 m³ h⁻¹ was applied for 24 h, sampling a total volume of around 720 m³. A total of 49 compounds were tentatively identified using very restrictive criteria regarding exact mass, retention time, isotopic profile and both MS² and MS³ spectra. Pesticides, pharmaceutical active compounds, drugs, plasticizers and metabolites were the most identified compounds. To verify whether the developed methodology was suitable, 11 substances were checked with their analytical standards and all of them were confirmed. Different profiles for industrial, rural and urban areas were examined. The Principal Component Analysis (PCA) model allowed us to separate the obtained data of the three assessed area. When the profiles obtained in the three evaluated areas were compared using a Volcano plot (the rural area was taken as reference), 11 compounds were confirmed as being discriminant: three of them (3-hydroxy-2-methylpyridine, 3-methyladenine and nicotine) were more likely to be found in industrial sites; ten compounds (3-hydroxy-2-methylpyridine, 3-methyladenine, azoxystrobin, cocaine, cotinine, ethoprophos, imidacloprid, metalaxyl-M, nicotine and pyrimethanil) were more probable in the case of urban sites; finally, triisopropanolamine was more likely to be detected in rural locations.

Synthetic cannabinoids receptor agonists (SCRAs) are often almost completely metabolised, and hence their pharmacokinetics should be carefully evaluated for determining the most adequate biomarker in toxicological analysis. Two structurally related SCRAs, AMB-FUBINACA and AMB-CHMICA, were selected to evaluate their in vivo metabolism and pharmacokinetics using male Sprague-Dawley rats. Brain, liver, kidney, blood (serum) and urine samples were collected at different times to assess the differences in metabolism, metabolic reactions, tissue distribution and excretion. Both compounds experimented O-demethyl reaction, which occurred more rapidly for AMB-FUBINACA. The parent compounds and O-demethyl metabolites were highly bioaccumulated in liver, and were still detected in this tissue 48 h after injection. The different indazole/indole N-functionalisation produced diverse metabolic reactions in this moiety and thus, different urinary metabolites were formed. Out of the two compounds, AMB-FUBINACA seemed to easily cross the blood-brain barrier, presenting higher brain/serum concentrations ratio than AMB-CHMICA.

There is an increasing need for comparable and harmonized retention times (t_R) in liquid chromatography (LC) among different laboratories, to provide supplementary evidence for the identity of compounds in high-resolution mass spectrometry (HRMS)-based suspect and nontarget screening investigations. In this study, a rigorously tested, flexible, and less system-dependent unified retention time index (RTI) approach for LC is presented, based on the calibration of the elution pattern. Two sets of 18 calibrants were selected for each of ESI+ and ESI-based on the maximum overlap with the retention times and chemical similarity indices from a total set of 2123 compounds. The resulting calibration set, with RTI set to range between 1 and 1000, was proposed as the most appropriate RTI system after rigorous evaluation, coordinated by the NORMAN network. The validation of the proposed RTI system was done externally on different instrumentation and LC conditions. The RTI can also be used to check the reproducibility and quality of LC conditions. Two quantitative structure–retention relationship (QSRR)-based models were built based on the developed RTI systems, which assist in the removal of false-positive annotations. The applicability domains of the QSRR models allowed completing the identification process with higher confidence for substances within the domain, while indicating those substances for which results should be treated with caution. The proposed RTI system was used to improve confidence in suspect and nontarget screening and increase the comparability between laboratories as demonstrated for two examples. All RTI-related calculations can be performed online at http://rti.chem.uoa.gr/.

Laboratory wastes containing Cd²⁺ and water polluted by pharmaceuticals represent an environmental concern. In this work, a proof concept, consisting of the use of teaching-laboratory wastes to synthesize CdS and its subsequent use as a photocatalyst to degrade fluoroquinolone antibiotics, was developed. The CdS was prepared by extraction with thioacetamide and calcination (at 450 °C) and characterized using several techniques. The photocatalytic activity of the CdS, to degrade levofloxacin and norfloxacin, was tested, and the routes involved in the process and the primary transformations of the fluoroquinolones were established. Moreover, the ability of CdS-photocatalysis to eliminate levofloxacin in simulated matrices of fresh urine and hospital wastewater was evaluated. The characterization analyses indicated that the CdS semiconductor was synthesized successfully. Effectively, the CdS acted as a photocatalyst toward degradation of levofloxacin, involving the action of superoxide anion radical, holes, and singlet oxygen mainly. The process induced transformations on the methyl-piperazyl moiety, plus hydroxylation of the fluoroquinolone nucleus on levofloxacin. Additionally, CdS-photocatalysis was highly selective for the elimination of the target pollutant in both tested matrices. Our research indicated the good potentiality of recycling teaching-laboratory wastes to generate photocatalysts to degrade organic pollutants. This work was presented at 4° Congreso Colombiano de Procesos Avanzados de Oxidación (4CCPAOx).

This paper provides scientific results from a European LIFE project carried out in the Valencian region of Spain during the 2017 to 2018 time frame. In 2018, more than 60,000 tons of pesticides were commercialized in Spain, with approximately 15% destined for Valencian crops. In order to improve the air quality in the agricultural areas of this region, an innovative cropping system based on irrigation was developed and compared to conventional treatments based on hand-spray and turbo application. After applying conventional treatments to five types of crops (citrus, persimmon, nectarine, watermelon, and other stone fruits), a total of 13 active substances were detected in the air. The same active substances were applied to crops using the novel irrigation system, and no pesticide was detected in the air. Moreover, applicator and bystander populations in the region were assessed for their risk of inhalation exposure to pesticides, and no risk was found when either of the techniques, the innovative and the conventional agricultural one, were applied.