Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma

Capecitabine is an important oral fluoropyrimidine anticancer drug. The purpose of this study was to overcome limitations of previously reported methods and propose an optimized and widely available tool for analysis of capecitabine in human plasma. The simplification of the liquid-liquid extraction procedure involved elimination of unnecessary addition of phosphoric acid and reduction of the extraction solvent volume. The use of voriconazole as the internal standard, combined with gradient elution and on-line wavelength switching, assured very high within- and between-run precision of results (relative standard deviation <7.1% for lower limit of quantification) and enabled the reduction of the total chromatographic run time to 8 min. The calibration curve was linear within the range of 0.05–10.00 μg/mL and the method selectivity was confirmed in the presence of capecitabine metabolites. All validation parameters met the acceptance criteria set by international regulatory guidances, which proves that the method leads to reliable results. The method may be applied in human pharmacokinetic studies, for the regulatory purposes and therapeutic drug monitoring.