Abstract
We describe a high performance liquid chromatography (HPLC) method that separates two of the currently licenced tyrosine kinase inhibitors (TKIs); nilotinib (AMN107, Tasigna) and imatinib (STI571, Glivec), together with its main metabolite, CGP-74588, from human plasma. After solid phase extraction the drug mix was separated through a Gemini C6-phenyl column (150 mm x 4.6mm, i.d.; 5 microm) (Phenomenex), UK) under isocratic mobile phase conditions of methanol:50mM ammonium acetate (pH 8) (65:35, v/v) with ultra-violet (UV) detection at 260 nm wavelength. For all compounds the intra-day coefficient of variation and bias were <3% and <5% respectively; and inter-day were <4% and <9%. This simple and novel method may be used to quantify levels of TKIs when used alone or in combination with drug treatments for clinical samples.
Copyright 2009 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Validation Study
MeSH terms
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Antineoplastic Combined Chemotherapy Protocols / analysis
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Antineoplastic Combined Chemotherapy Protocols / blood
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Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
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Benzamides
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Blood Chemical Analysis / methods*
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Blood Chemical Analysis / standards
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Calibration
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Chromatography, High Pressure Liquid / methods
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Chromatography, High Pressure Liquid / standards
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Circadian Rhythm / physiology
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Humans
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Imatinib Mesylate
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Limit of Detection
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Piperazines / administration & dosage
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Piperazines / analysis*
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Piperazines / blood
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Piperazines / isolation & purification
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Piperazines / metabolism
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Piperazines / pharmacokinetics
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Plasma / chemistry*
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / analysis
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Protein Kinase Inhibitors / blood
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Protein Kinase Inhibitors / pharmacokinetics
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Pyrimidines / administration & dosage
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Pyrimidines / analysis*
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Pyrimidines / blood
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Pyrimidines / isolation & purification
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Pyrimidines / metabolism
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Pyrimidines / pharmacokinetics
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Quality Control
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Sensitivity and Specificity
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Spectrophotometry, Ultraviolet / methods
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Spectrophotometry, Ultraviolet / standards
Substances
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Benzamides
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CGP 74588
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Piperazines
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Protein Kinase Inhibitors
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Pyrimidines
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Imatinib Mesylate
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nilotinib