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 μg/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.