Hydrophilic interaction liquid chromatography/tandem mass spectrometry for the simultaneous determination of dasatinib, imatinib and nilotinib in mouse plasma

Hydrophilic interaction liquid chromatography (HILIC) interfaced with atmospheric pressure ionization (API) sources and a tandem mass spectrometer (MS/MS) was developed for the simultaneous determination of dasatinib, imatinib and nilotinib in mouse plasma samples. The retention profiles of all analytes on several silica stationary phases under HILIC conditions were explored. The influences of experimental factors such as the compositions of mobile phases on the chromatographic performance and the ionization efficiency of all analytes in positive ion mode were investigated. The applicability of the proposed HILIC/MS/MS approach following a protein precipitation procedure for the quantitative determination of dasatinib, imatinib and nilotinib at low nano-mole levels was examined with respect to assay specificity and linearity. The analytical results obtained by various HILIC/MS/MS approaches were found to be in good agreement with those obtained by reversed-phase liquid chromatography/tandem mass spectrometry (RPLC/MS/MS) methods in terms of assay sample throughputs, sensitivity and accuracy. Furthermore, the potential of matrix ionization suppression on the proposed HILIC/MS/MS systems was investigated using the post-column infusion technique. Copyright (C) 2009 John Wiley & Sons, Ltd.