The impact of the dSPE lipid depletion on selected xenobiotics, especially more lipophilic lansoprazole, amitriptyline, terbinafine and diclofenac, eluting across the whole retention range and added to the sample before processing was assessed by calculating their recovery at four different concentrations (Table ). dSPE-treated and sham control samples demonstrated no significant difference in mean signal intensities for the exemplary set of xenobiotics with recoveries ranging 80-110%, except for ibuprofen. Its mean intensity between sham and dSPE-treated samples varied significantly at different concentrations. Ibuprofen elutes after 10 min, co-eluting with the lipophilic fraction, which may produce an unstable signal due to mutual ion suppression and high background signal (in agreement with the observations made during the extraction solvent optimization).