A method to quantify several tyrosine kinase inhibitors in plasma by micellar liquid chromatography and validation according to the European Medicines Agency guidelines

A procedure based on micellar liquid chromatography has been developed to monitor five tyrosine kinase inhibitors in plasma, prescribed against several kinds of cancer: erlotinib, imatinib, sunitinib, sorafenib and lapatinib. The sample was diluted in a micellar solution and directly injected, thus clean-up steps were not required. The analytes were resolved without interferences in <20 min using a C18 column and a mobile phase of 0.13 M SDS-4% 1-butanol, buffered at pH 3.5, running under isocratic mode at 1 mL/min. The detection was performed by UV-visible absorbance, using a wavelength program to maximize the signal-to-noise ratio. The method was validated following the guideline of the European Medicines Agency in terms of: selectivity, calibration range (0.05-5 mu g/mol), linearity (r(2) > 0.990), limit of detection (15-35 ng/mL), carry-over effect, accuracy (-10.4 to +11.0%), precision (< 9.2%), matrix effect, robustness (< 8.4%) and stability. The procedure is rapid, easy-to-handle, uses a low amount of toxic chemical provide reliable results. Finally, the method was successfully used to analyze the studied tyrosine kinase inhibitors in plasma from cancer patients. (C) 2015 Elsevier B.V. All rights reserved.