Direct salting-out assisted liquid–liquid extraction (SALLE) from human blood: Application for the analysis of tyrosine kinase inhibitors

Abstract

The application of salting-out assisted liquid–liquid extraction (SALLE) is proposed for the first time for the extraction of drugs directly from whole blood samples prior to their analysis by capillary electrophoresis or liquid 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 in appropriate volumes to precipitate proteins. After swirling and centrifugation, sodium chloride was added to the blood-ACN mixture to induce a two phases separation. TKIs were efficiently extracted in the upper mostly organic phase which was directly analyzed by CE-UV or LC-UV. SALLE-CE-UV and SALLE-LC-UV methodologies offer 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.