| Summary: | A sensitive, rapid, simple and economical ultra-performance liquid chromatographyâtandem mass spectrometric method (UPLCâMS/MS) was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard (IS). Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A (aqueous phase: 0.15% formic acid and 0.05% ammonium acetate) and B (organic phase: acetonitrile) (A:B=40:60, v/v). The flow rate was 0.25Â mL/min and the total run time was 6Â min. The multiple reaction monitoring (MRM) transitions, m/z 494.5â394.5 for imatinib, 488.7â401.5 for dasatinib, 530.7â289.5 for nilotinib and 528.5â403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6â5250.0Â ng/mL for imatinib, 2.0â490.0Â ng/mL for dasatinib, and 2.4â4700.0Â ng/mL for nilotinib. The method showed acceptable results on sensitivity, specificity, recovery, precision, accuracy and stability tests. This UPLCâMS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentrations among the SLC22A5 â1889T>C or SLCO1B3 699G>A genotypes (P>0.05). This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors (TKIs). Keywords: UPLCâMS/MS, Imatinib, Dasatinib, Nilotinib, Polymorphism
|
|---|