Simultaneous quantification of imatinib and CGP74588 in human plasma by liquid chromatography-time of flight mass spectrometry (LC-TOF-MS)
Imatinib mesylate is widely used for the treatment of different types of cancer, such as chronic myelogenous leukemia and gastrointestinal stromal tumors. It is a tyrosine kinase inhibitor that binds to the active site of the enzyme inhibiting it. In clinical toxicology, a fast and sensitive quantification method for monitoring the imatinib concentration in blood can be very useful for personalized treatments. The aim of this study was to propose an alternative novel analytical method (LC-TOF-MS) for the quantification of intracellular imatinib and its main metabolite in human plasma. The method is simple and fast. It has sufficient sensitivity for the quantification of imatinib and its main metabolite CGP74588 in a smaller volume of plasma. The linearity of the method was evaluated over the range of concentrations (0.02–5 μg mL−1) of imatinib and CGP74588 in human plasma. The correlation coefficients (r2) were close to 1 for both analytes. The limit of quantification was 0.02 μg mL−1 for both imatinib and CGP74588. A number of (>50) chronic myelogenous leukemia patient plasma samples have been analyzed by this method obtaining values ranging from 0.19–4.53 and 0.03–0.84 μg mL−1 for imatinib and CGP74588, respectively. This novel method allows a specific, sensitive and reliable simultaneous determination of intracellular imatinib and CGP74588 in a single chromatographic run, which is suitable for routine clinical practice.