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EXTRACTION PROCESS ASSESSMENT AND LC-MS ANALYSIS OF TWO TYROSINE KINASE INHIBITORS IN HUMAN PLASMA

SIMONA-DANIELA NEAMȚU 1, COSTEL-VALENTIN MANDA 1*, MIHAIL-VIRGIL
BOLDEANU 2, IONELA ROTARU 2, JOHNY NEAMȚU 1, ANDREI BIȚĂ 1, OCTAVIAN
CROITORU 1, DANIELA MARIA CALUCICĂ 1

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The class of tyrosine kinase inhibitors (TKIs) is represented by a group of compounds which are currently used in the treatment of different types of cancer. As plasma concentration profiles of these drugs reveal a large interindividual variability, therapeutic drug monitoring (TDM) might be necessary to adjust the therapeutic protocol. With this purpose, we developed and validated a simple and accurate method for determining plasma concentrations for two TKIs. Solid phase extraction (SPE) using Oasis PRiME HLB® cartridges was used for plasma sample preparation procedure. The method provided clean extracts with a recovery extraction of more than 85%. Separation was achieved by high-performance liquid chromatography (HPLC), using a C18 (4.6 x 50 mm) column, with a gradient elution of ammonium formate-acetonitrile as mobile phase. Detection was performed by mass spectrometry (MS) in Single Ion Recording (SIR) mode. Intra-day and interday precision data for both analytes were 3.8 - 7.2% and 3.6 - 7.4%, respectively. Calibration curves were both linear between 2 and 400 ng/mL with a correlation coefficient higher than 0.998. The LC-MS method was used to quantify both TKIs in human plasma in routine analysis. The method was applied to TDM of ibrutinib and ruxolitinib and may help physicians for dose adjustment.