Intensive horticulture and the reuse of poultry litter (PL) can introduce mixtures of pesticides and veterinary pharmaceuticals into adjacent waters. A multi-matrix study was conducted at eight stream sites in the Cinturón Hortícola Platense (Argentina) across three sampling campaigns. Surface water, suspended particulate matter (SPM), bottom sediments, and aquatic macrophytes were analyzed by LC-MS/MS. Target compounds included ionophore polyether antibiotics (IPAs), selected pesticides, avermectins and the fluoroquinolone enrofloxacin. Monensin was the most frequently detected IPA. Glyphosate and its metabolite AMPA were ubiquitous across matrices, while chlorpyrifos and its metabolite TCP were widespread in water and sediments. Prometryn and tebuconazole were consistently observed across campaigns, whereas avermectins and enrofloxacin were not detected. Macrophytes accumulated several target compounds, supporting their role as integrators of contamination. Pseudo-partition coefficients (water-sediment, water-SPM) indicated a preferential association of monensin, glyphosate, and AMPA with solid phases. Principal component analysis linked monensin with organic-matter and nutrient proxies, consistent with PL-driven runoff. A screening environmental risk assessment indicated very high risk for chlorpyrifos in water and sediment, and low risk for IPAs at observed levels. Findings highlight the complex contamination arising from horticultural practices that combine animal-derived soil amendments with pesticide applications. Sampling strategies should include transformation products and macrophyte biomonitoring, as aquatic plants can indicate agricultural contamination. The results provide actionable evidence to guide monitoring and mitigation efforts in peri-urban horticulture, emphasizing the importance of vegetated buffers, improved PL handling, and comprehensive surveillance that includes metabolites.
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