QUANTITATIVE ANALYSIS OF SORAFENIB AND NILOTINIB IN HUMAN PLASMA BY SPE-LC-MS
MONICA DENISA ELENA POPESCU 1, COSTEL-VALENTIN MANDA 1*, DANIELA MARIA CALUCICĂ 1, AMELIA MARIA GĂMAN 2, JOHNY NEAMȚU 1, ANDREI BIȚĂ 1, OLIVIA GAROFIȚA MATEESCU 2, SIMONA-DANIELA NEAMȚU 1, ȘTEFAN RĂILEANU 3, LILIANA STANCA 2, OCTAVIAN CROITORU 1
1Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Petru Rareș Street, 200638, Craiova, Romania
2Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Petru Rareș Street, 200638, Craiova, Romania
3“Filantropia” Clinic Oncology Municipal Hospital, 1 Filantropiei Street, 200143 Craiova, Romania
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Sorafenib and nilotinib are two tyrosine kinase inhibitors (TKIs) used in the treatment of cancer. Plasmatic levels of the drugs show an important variability, so determining plasma concentration of the drugs, benefits in cancer treatment can be improved. Most papers published so far in the literature use protein precipitation followed by liquid chromatography - tandem mass-spectrometry (LC-MS/MS) as separation and detection method. With this work, we propose an alternative method for the analysis of both TKIs in human plasma. Solid phase extraction (SPE) involving Oasis PRiME HLB® cartridges was our choice for plasma “clean-up” procedure. Extraction recoveries were at least 85%. Chromatography was performed by an ultra-high-performance liquid chromatographic system (UHPLC), using a C18 (4.6 x 50 mm) column and a mobile phase consisting of ammonium acetate/acetic acid-acetonitrile gradient elution. Detector was a simple mass spectrometer (MS) in Single Ion Recording (SIR) mode. Intra- and inter-day precision data for both TKIs were 3.8 - 7.6% and 4.5 - 8.8% for sorafenib and nilotinib, respectively. Sorafenib and nilotinib calibration curves were linear between 500 and 20000 ng/mL and 5 and 5000 ng/mL respectively, with correlation coefficients higher than 0.998. Analytes were determined in a 15 min run-time. The validated LC-MS method was applied in real human plasma routine analysis. This method may improve dose adjustment of the drugs in patients involved in cancer therapy.