title: Routine therapeutic drug monitoring of tyrosine kinase inhibitors by HPLC-UV or LC-MS/MS methods.
abstract: 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.
authors.affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan. Electronic address: m-miura@hos.akita-u.ac.jp.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.affiliation: Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology / Q000379:methods; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D040901:Proteomics / Q000379:methods; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases
keywords: Dasatinib; HPLC; Imatinib; LC–MS/MS; Nilotinib