Journal
BIOMEDICAL CHROMATOGRAPHY
Volume 27, Issue 4, Pages 466-476Publisher
WILEY
DOI: 10.1002/bmc.2814
Keywords
LC-MS; MS; tyrosine kinase inhibitors; therapeutic drug monitoring
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To support pharmacokinetic-guided dosing in individual patients, a fast and accurate method for simultaneous determination of anticancer tyrosine kinase inhibitors (TKIs) dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, sorafenib and sunitinib in human plasma was developed using high-performance liquid chromatography and detection with tandem mass spectrometry (HPLC-MS/MS). Stable isotopically labeled compounds of the eight different TKIs were used as internal standards. Plasma proteins were precipitated and an aliquot of supernatant was directly injected onto a reversed phase chromatography system consisting of a Gemini C18 column (50x2.0mm i.d., 5.0 mu m particle size) and then compounds were eluted with a gradient. The outlet of the column was connected to a triple quadrupole mass spectrometer with electrospray interface. Ions were detected in the positive multiple reaction monitoring mode. This method was validated over a linear range from 20.0 to 10,000ng/mL for erlotinib, gefitinib, imatinib, lapatinib, nilotinib and sorafenib, and from 5.00 to 2500ng/mL for dasatinib and sunitinib. Results from the validation study demonstrated good intra- and inter-assay accuracy (<13.1%) and precision (10.0%) for all analytes. This method was successfully applied for routine therapeutic drug monitoring purposes in patients treated with the investigated TKIs. Copyright (c) 2012 John Wiley & Sons, Ltd.
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