*2.1. Materials*

The target pharmaceuticals were purchased from Sigma-Aldrich (Madrid, Spain) and presented purities over 97%. Three internal standards (IS), atenolol-d7 (Toronto Research Chemical Inc, Toronto, Canada), ibuprofen-d3 (Sigma-Aldrich, Madrid, Spain), and sulfamethoxazole-d4 (Dr. Ehrenstorfer GmbH, Ausgburg, Germany) were used to minimize the matrix e ffect of the studied samples.

Stock solutions were prepared at 1000 mg·L−<sup>1</sup> by dissolving the compound in high-purity methanol. These solutions were stored in glass-stoppered bottles at –20 ◦C prior to use. Working solutions were prepared daily from a stock mixture of 10 mg·L−<sup>1</sup> by diluting proper quantities of the stock mixture in LC–MS grade water.

The mobile phase of UHPLC–MS/MS system was prepared using LC–MS grade methanol and water, both purchased from Panreac (Barcelona, Spain) as well as the modifiers of the mobile phase. The Milli-Q water used in the wash step of SPE was obtained using a water purification system of Millipore (Bedford, MA, USA)
