Chlorothiazide

All anti‐doping programmes face financial constraints and monitoring trends in medication use or abuse in a population of racehorses can be difficult and expensive. Obtaining biological samples is the primary method of anti‐doping control in individual horses or stables of horses but can be invasive and expensive. Another important practice of anti‐doping control has been the confiscation of used and filled syringes by regulators for individual forensic analysis. Pooled samples testing involves the testing of multiple individual samples together as one composite sample. This pooled sample approach has been employed to gather information concerning populations' exposure to substances and infectious agents including the analysis of samples of wastewater (a large, pooled sample) that have been used during the pandemic to monitor the presence of new COVID variants. Moreover, pooled samples of urine and wastewater have been used to monitor for recreational drug use and for the presence of new psychoactive substances in cities and large events. This approach has been credited with providing timely insight in the trends of illicit drugs use. To be effective, an anti‐doping programme should not be predictable to avoid being defeated by countermeasures; therefore, the implementation of new methods is considered essential. A new pooled sampling technique using confiscated groups of used syringes and needles including biomedical sharps containers obtained from veterinarians and other horse racing industry participants has been employed over several years in Ontario, Canada. These containers held needles used to administer substances to racehorses along with syringes and other debris. The analysis of the wash provided a timely insight of medications being administered in horses, and substances present at racetracks and training centres including substances predominantly of human use and abuse. Sharp containers confiscated from veterinarians and trainers provided insight into injectable medications administered at numerous stables and to hundreds of horses.

Water contamination by micropollutants is a global issue, yet there is limited information from low-income regions. To address this, we evaluated surface water quality in rapidly growing Sub-Saharan area of Malawi lacking wastewater treatment. Integrated assessment of passive sample extracts representing wet and dry seasons combined effect-based approach with in vitro bioassays, target and non-target chemical analyses (NTS). It revealed specific contamination profiles characterized by high concentrations of numerous pollutants, frequent exceedances of Predicted No-Effect Concentrations, and concerning levels of certain insecticides (chlorpyrifos, pirimiphos-methyl) and pharmaceuticals (sulfamethoxazole, trimethoprim, diclofenac). Proposed threshold values were exceeded for estrogenicity, androgenicity, aryl hydrocarbon receptor-mediated activity, thyroid hormone receptor agonism, and transthyretin (TTR) binding inhibition (highest effect-based trigger value exceedance, over 600-fold), which indicates risks to aquatic life. The combination of TTR pull-down assay, NTS, and bioassays enabled the isolation and identification of active compounds, including previously unreported TTR ligands 4-hydroxychlorothalonil (pesticide metabolite) and chlorothiazide (diuretic). Linear alkylbenzene sulfonates and related features contributed most significantly to TTR binding inhibition. This study introduces novel analytical approaches to address challenging groups of surfactants occurring in technical mixtures containing multiple branched isomers. The results underscore the added value of implementing effect-based assessment in understudied regions and the challenges posed by transformation products and technical mixtures lacking standards and reference spectra in NTS libraries. Our findings emphasize the need to expand MS/MS spectral libraries by incorporating metabolites and transformation products. The study highlights the impacts and risks of untreated wastewater discharges in regions affected by climatic and socio-economic pressures.