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 bi...

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Bibliographic Details
Published in:Drug metabolism and pharmacokinetics 2016-02, Vol.31 (1), p.12-20
Main Authors: Miura, Masatomo, Takahashi, Naoto
Format: Article
Language:English
Subjects:
Chromatography, High Pressure Liquid
Computational Biology - methods
Dasatinib
Drug Monitoring - methods
HPLC
Humans
Imatinib
LC–MS/MS
Nilotinib
Protein Kinase Inhibitors - chemistry
Protein-Tyrosine Kinases - antagonists & inhibitors
Proteomics - methods
Spectrophotometry, Ultraviolet
Tandem Mass Spectrometry
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Summary: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.
ISSN:1347-4367
1880-0920
DOI:10.1016/j.dmpk.2015.09.002