Abstract
The objective of the present work was to evaluate the relevance of capillary electrophoresis (CE) method for the quantification of tyrosine kinase inhibitors (TKIs) in human plasma in the context of TDM. Four TKIs were selected for this study: imatinib mesylate, erlotinib hydrochloride, lapatinib ditosylate and sorafenib.A fast, simple and cost effective CZE-UV methodology for the quantification of imatinib in plasma was first developed using simply ACN precipitation as sample preparation before analysis. A complete study was performed to understand the electrophoretic behavior of imatinib in the presence of salt (from plasma) and ACN in the sample matrix. Then, a thorough study was performed to optimize an easy to use and performing sample pretreatment methodology based on salting-out assisted liquid-liquid extraction (SALLE) for the four TKIs from human plasma. SALLE, which is based on adding high concentration of salt to two miscible liquids, allows to extract in one step TKIs from plasma in an ACN phase with high recovery. The extracted TKIs can then be directly injected for further CZE-UV analysis. The use of ACN as extraction solvent allows to inject up to 80% of the capillary effective volumes. This allows in-line sample concentration through electrophoretic stacking mechanisms. In the perspective of routine use, the SALLE-CZE-UV methodology was fully automated. The analytical performances obtained for the four TKIs are fully suitable with TDM requirements. Finally, the SALLE-CZE-UV was successfully applied for the extraction and analysis of the four TKIs directly from human blood. All the present developments prove that CE is a relevant technique to address many TDM issues.