Determination of anticancer-drugs in blood plasma with ultra performance liquid chromatography with massdetection

Abstract

The purpose of this study was to develop and validate methods of quantitative determination of
anticancer drugs from the list of VED drugs for the 2012-2014 (capecitabine and its active metabolite
5-fluorouracil, temozolomide, imatinib) in human plasma for further application in pharmacokinetic studies.
To conduct the study 3 bioanalytical methods for determining 3 the following drugs in plasma:
capecitabine (5-fluorouracil), temozolomide and imatinib were developed and validated. Liquid
chromatograph Waters Acquity Systems with a quadrupole mass detector was used for this study. As the
stationary phase column was used Acquity UPLC BEH C18, 50*2,1 mm, 1.7 μm. Sample preparation was
performed using protein precipitation. Detection were carried out with the ES+ for the relevant characteristic
ions.
The developed methods were validated in accordance with the guidelines by the FDA, EMA and the
Russian leadership on the examination of drugs edited by Mironov. All methods satisfies the documents
requested for selectivity, linearity, accuracy, precision, limit of quantification, sample transfe, the stability,
the matrix effect. Analytical methods developed for a range of capecitabine (0.1-10 μg/ml) with 5-
fluorouracil metabolite (0.05-5 μg /ml), temozolomide (0.1-10 μg/ml) and imatinib (50-2000 ng/mL) in
human plasma. Methods validated in terms of: selectivity, linearity, accuracy, precision, limit of
quantification. The methods developed can be applied to the analysis of pharmacokinetics and bioavailability
of drugs.