Routine therapeutic drug monitoring of tyrosine kinase inhibitors by HPLC-UV or LC-MS/MS methods

Analytical methods using high performance liquid chromatography coupled to ultraviolet detection (HPLC-UV) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) have been reported for the quantification of oral tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, and dasatinib in biological fluids. An LC-MS/MS method can simultaneously assay multiple TKIs and their metabolites with high sensitivity and selectivity for low plasma concentrations less than 1 ng/mL. For quantification of imatinib, nilotinib, and dasatinib, a limit of quantification (LOQ) of less than 10 ng/mL, 10 ng/mL, and 0.1 ng/mL, respectively, in the clinical setting is necessary. Because simpler and more cost-efficient methodology is desired for clinical analysis, plasma concentrations of imatinib and nilotinib (target trough concentrations of 1000 ng/mL and 800 ng/mL, respectively) could be assayed by an HPLC-UV method after comparison with results obtained from the standard LC-MS/MS method. However, in the quantification of dasatinib, the LC-MS/MS method that has high sensitivity and selectivity and is free from interference by endogenous impurities is superior to the HPLC-UV method. Highly precise analytical methods are needed for individualized treatment via dose adjustment of oral anticancer drugs, in particular those with low target plasma concentrations less than 10 ng/mL.