Sample preparation is one of the most important step in bioanalysis and it is crucial to ensure appropriate biological interpretation. In biological samples there are present, with the analyte, numerous other components which can reduce the sensitivity and selectivity of bioanalysis, as well as damage the analytical instrument. Solid phase extraction is one of the major sample preparation methods that allows removal of interferences and concentrating the target analytes. The aim of this study was to examine the efficiency of various types of sorbens for solid phase extraction as a sample preparation method for determination of azathioprine, 6-thioguanine and folic acid in plasma samples. Azathioprine and 6-thioguanine are immunosuppresants, one of the major group of medicines used in the treatment of inflammatory bowel disease. Pacients with IBD are at risk for folate deficiency, therefore it is usefull to monitor not only drugs but also the level of folate which shows the need for their supplementation. The following sorbents were tested: modified silica gel (C8 and C18), polymer sorbent (HLB) and innovative sorbent: Phree Phospholipid Removal. Examined modified silica gel and polymer sorbent have not successfully separated the interferences from the selected analytes. Therefore all of them are not suitable for the preparation of plasma samples. Innovative selective sorbent Phree Phospholipid Removal allows simultaneous removal of protein and phospholipids from a biological sample. The preparation of the sample with this sorbent removes the negative chromatographic effects of interferences such as ion suppression, reduced analyte sensitivity and decreased column life - time. This sorbent is most suitable for the preparation of plasma sample for analysis. Analytical recovery was near 100%.