The application of salting-out assisted liquid–liquid extraction (SALLE) is proposed for the first time for theextraction of drugs directly from whole blood samples prior to their analysis by capillary electrophoresis orliquid chromatography coupled to UV detection. Four anticancer drugs, i.e. tyrosine kinase inhibitors (TKIs),were selected as proof-of-concept analytes. First, blood samples containing TKIs were mixed with acetonitrile inappropriate volumes to precipitate proteins. After swirling and centrifugation, sodium chloride was added to theblood-ACN mixture to induce a two phases separation. TKIs were efficiently extracted in the upper mostlyorganic phase which was directly analyzed by CE-UV or LC-UV. SALLE-CE-UV and SALLE-LC-UV methodologiesoffer many advantages by combining fast extraction procedure and separation efficiency in a simple cost-effective way. Performances of both methodologies were evaluated in terms of extraction efficiency, LOQ, LOD,specificity, repeatability, total analysis time and cost per analysis