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AbstractGlobal climate changes cause water scarcity in many regions, and the sustainable use of recycled water appears crucial, especially in agriculture. However, potentially hazardous compounds such as pharmaceuticals can enter the food chain and pose severe risks. This paper aims to study the presence of selected pharmaceutical active compounds (PhACs) and their metabolites in crops grown in aeroponic conditions and evaluate the potential of PhAC plant uptake. A solvent extraction with an acidified mixture of acetonitrile and water followed by LC-HRMS was developed and validated for quantifying nine pharmaceuticals and their nine metabolites in three plants. We aimed for a robust method with a wide linear range because an extensive concentration range in different matrices was expected. The developed method proved rapid and reliable determination of selected pharmaceuticals in plants in the wide concentration range of 10 to 20,000 ng g−1 and limit of detection range 0.4 to 9.0 ng g-1. The developed method was used to study the uptake and translocation of pharmaceuticals and their metabolites in plant tissues from an aeroponic experiment at three different pH levels. Carbamazepine accumulated more in the leaves of spinach than in arugula. On the other hand, sulfamethoxazole and clindamycin evinced higher accumulation in roots than in leaves, comparable in both plants. The expected effect of pH on plants' uptake was not significant.

Abstract
The accumulation of six pharmaceuticals of different therapeutic uses has been thoroughly investigated and compared between onion, spinach, and radish plants grown in six soil types. While neutral molecules (e.g., carbamazepine (CAR) and some of its metabolites) were efficiently accumulated and easily translocated to the plant leaves (onion > radish > spinach), the same for ionic (both anionic and cationic) molecules seems to be minor to moderate. The maximum accumulation of CAR crosses 38,000 (onion), 42,000 (radish), and 7000 (spinach) ng g−1 (dry weight) respectively, in which the most majority of them happened within the plant leaves. Among the metabolites, the accumulation of carbamazepine 10,11-epoxide (EPC — a primary CAR metabolite) was approximately 19,000 (onion), 7000 (radish), and 6000 (spinach) ng g−1 (dry weight) respectively. This trend was considerably similar even when all these pharmaceuticals applied together. The accumulation of most other molecules (e.g., citalopram, clindamycin, clindamycin sulfoxide, fexofenadine, irbesartan, and sulfamethoxazole) was restricted to plant roots, except for certain cases (e.g., clindamycin and clindamycin sulfoxide in onion leaves). Our results clearly demonstrated the potential role of this accumulation process on the entrance of pharmaceuticals/metabolites into the food chain, which eventually becomes a threat to associated living biota.