Xenobiotics are defined as substances foreign to a living organism, such as pharmaceuticals, pesticides, some food additives, cosmetics and industrial waste. Using xenobiotics in unknown and uncontrolled quantities is potentially harmful to the environment and the living world in general. It is therefore very important to develop methods of their monitoring and determination. In this paper, a mixture of ten pharmaceuticals classified to different groups have been quantified: antibiotics (azithromycin, cefdinir, erythromycin, clarithromycin, nitrofurantoin), antiemetics (metoclopramide), antihelmintics or antiparasitics (albendazole, febantel, praziquantel) and chemotherapeutic (hydroxychloroquine). The aim of this paper is to optimize the conditions for ultrasonic extraction and matrix solid phase dispersion (MSPD) of ten xenobiotics from activated sludge. Nine experiments were performed using ultrasonic extraction (USE). Parameters which were optimized were the concentration of standard solution, mass of the sample, solvent or mixture of solvents for elution and solvents for dissolving the dry residue, while with MSPD five experiments were performed and solvent/mixture of solvents for elution were optimized. The extracts were analysed by high-performance liquid chromatography with diode array detector (HPLC-DAD). The method was validated by determining repeatability, renewability, limit of detection and limit of quantification. The best results for the USE were achieved with a standard solution of 10 mg/L and 0,5 grams of sample. The best solvent system is acetone:methanol = 1:1. Also, by using the mobile phase as the solvent for dissolving the dry residue, higher yields for some of the xenobiotics were achieved. For the MSPD method, the best pure solvents are methanol and ethanol, and the best systems are 1-propanol:water = 60:40 and methanol:water = 80:20, which extracted all xenobiotics. Since the USE and the MSPD did not achieve the desired recoveries (over 50 % for all xenobiotics) it is necessary to carry out further experiments or try an alternative method of extraction.