期刊
CLINICA CHIMICA ACTA
卷 404, 期 2, 页码 134-139出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.cca.2009.03.042
关键词
Sunitinib; UV-Visible detection; Reversed-phase chromatography; Cancer patients; Therapeutic drug monitoring
Background: Sunitinib malate is a novel oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities. Only mass spectrometry detection is currently available to determine sunitinib in human plasma. The purpose of this study was to develop a simple and sensitive high-performance liquid chromatographic method with UV-Visible detection for quantification of sunitinib concentrations in human plasma. Methods: After a liquid-liquid extraction with ethyl acetate, sunitinib and ranitidine (internal standard) are separated on cyanopropyl column using a simple binary mobile phase of ammonium acetate buffer (20 mM; pH 6.8):acetonitrile (55:45.v/v). Samples were eluted isocratically at a flow rate of 1 mL/min throughout the 10 min run. Dual wavelength mode was used, with ranitidine monitored at 255 nm, and sunitinib at 431 nm. Results: The calibration was linear in the range 20-200 ng/mL. Inter- and intra-day coefficients of variation were less than 7%. This method is sensitive, accurate and selective. It has been successfully implemented to monitor trough sunitinib concentrations in plasma samples (n=39) from 14 unselected cancer patients treated with the recommended once daily dose of 50 mg or less. Conclusion: This method can be used in routine clinical practice to monitor plasma sunitinib concentrations in cancer patients treated with once daily administration. (C) 2009 Elsevier B.V. All rights reserved.
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