This study investigated the presence of pharmaceuticals in the water and sediment of Buffalo and Sundays River Estuary, South Africa. Extraction for water and sediment samples was achieved with solid-phase extraction and ultrasonic extraction methods, respectively. Quantification of the target analytes was done with UPLC-QTOF-MS. The pH of surface water in all the sampling sites (8.18–10.1) were above the WHO guideline (6.5). A good correlation was observed between the concentrations of analytes with organic matter and organic carbon. Results showed that carbamazepine exhibited the highest concentration (8.75 ± 1.45 μg/kg) of all the pharmaceuticals, while trimethoprim has the highest detection frequency with the highest concentration of 1.62 ± 0.83 μg/kg in the sediment samples. Sulfamethoxazole was below the detection limit in both estuaries. Calculated risk quotients revealed that carbamazepine and trimethoprim could be of potential risk, while caffeine may pose a very low risk to the aquatic organisms investigated. Proper monitoring of the runoff entering Buffalo Estuary is required, being the point of discharge of Buffalo River to the Indian Ocean. Also, the domestic waste discharge from residences in the surroundings of Sundays Estuary should be monitored.
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