期刊
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
卷 877, 期 32, 页码 4090-4096出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jchromb.2009.10.024
关键词
Axitinib; Erlotinib; Tyrosine kinase inhibitor; LC/MS/MS; Human plasma; Trans to cis isomerization
A bioanalytical assay for the new tyrosine kinase inhibitor axitinib was developed and validated. In addition, the light mediated trans to cis isomerization of this drug was investigated. For the quantitative assay, human plasma samples were pre-treated under light protection using protein precipitation with acetonitrile containing erlotinib as the internal standard. The extract was diluted with water and injected into the chromatographic system. The system consisted of a trifunctional bonded octadecyl silica column with isocratic elution using formic acid in a water-methanol mixture. The eluate was transferred into an electrospray interface with positive ionization and the analyte was detected and quantified using the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 0.2-200 ng/ml concentration range, the lowest level of this range being the lower limit of quantification. Within day precisions were 2.5-6%, between day precisions 4-9% and accuracies were between 91 and 106% for the whole calibration range. Light protected axitinib showed no isomerization and was shown to be chemically stable under all relevant conditions. Finally, the assay was successfully applied for a mouse tissue distribution study using mouse samples diluted with human plasma. (C) 2009 Elsevier B.V. All rights reserved.
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