期刊
CLINICA CHIMICA ACTA
卷 413, 期 1-2, 页码 143-149出版社
ELSEVIER
DOI: 10.1016/j.cca.2011.09.012
关键词
Tyrosine kinase inhibitors; Plasma; Quantification; Multi-parameter analysis; Liquid chromatography; Mass spectrometry
资金
- LOEWE-UGMLC initiative of the Hessian government
Background: Increasing numbers of tyrosine kinase inhibitors (TKIs) were studied and approved for therapy of malignancies and other diseases. The aim of this study was to develop and validate a specific, simple and rapid quantification method for various TKIs in human plasma. Methods: A simultaneous test for six TKIs (erlotinib, imatinib, lapatinib, nilotinib, sorafenib, sunitinib) was developed using liquid chromatography tandem mass spectrometry in a multiple reaction monitoring mode. After protein precipitation the specimens were applied to the HPLC system and separated using a gradient of acetonitrile containing 1% formic add with 10 mM ammoniumformiate on an analytic RP-C18 column. Results: The calibration range was 10-1000 ng/mL for sunitinib and 50-5000 ng/mL for the other TKIs with coefficients of determination >= 0.99 for all analytes. The intra- and inter day coefficients of variation were <= 15% and the chromatographic run time was 12 min. Plasma specimens were stable for measurement for at least 1 week at 4 C. Clinical applications of the assay are exemplarily discussed. Conclusions: This novel high-throughput method is suitable for specific simultaneous determination of different TKIs in routine clinical practice. (C) 2011 Published by Elsevier B.V.
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