Journal
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Volume 937, Issue -, Pages 33-43Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jchromb.2013.08.013
Keywords
LC-MS/MS; Tyrosine kinase inhibitors; Metabolites
Funding
- Stichting een gift voor GIST
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A sensitive, sophisticated and practical bioanalytical assay for the simultaneous determination of six tyrosine kinase inhibitors (imatinib, sunitinib, nilotinib, dasatinib, pazopanib, regorafenib) and two active metabolites (N-desmethyl imatinib and N-desethyl sunitinib) was developed and validated. For the quantitative assay, a mixture of three stable isotopes as internal standards was added to human serum, standards and controls. Thereafter, samples were pre-treated using protein precipitation with methanol. The supernatant was diluted with water and injected into an ultra pressure liquid chromatographic system with an Acquity TQ tandem mass spectrometry detector. The compounds were separated on an Acquity BEH C18 analytical column (100 mm x 2.1 mm ID, 1.7 mu m particle size) and eluted with a linear gradient system. The ions were detected in the multiple reaction monitoring mode. The lower limit of quantification and the linearity of all compounds generously met with the concentrations that are to be expected in clinical practice. The developed bioanalytical assay can be used for guiding TKI therapy in daily clinical practice as well as for investigator-initiated research. (c) 2013 Elsevier B.V. All rights reserved.
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