Capecitabine is a drug widely used in the treatment of breast and colorectal cancers which annualy caused over 458.000 and 608.000 deaths worldwide, respectively. The aim of the study was to develop the bioanalytical method to investigate bioequivalence of generic and reference medicinal products.

Sample preparation, based on simple liquid-liquid extraction [1], was optimized to reduce organic solvent consumption. HPLC analysis run time was only 8 min, comparing to 30 min reported previously [1]. On-line wavelength switching from 305 nm to 265 nm was applied for detection of low-cost and widely available voriconazole, which was first-ever used as internal standard. The method selectivity was confirmed in the presence of six main capecitabine metabolites. The stability studies of capecitabine in human plasma were preceded by the detailed stability studies of the active pharmaceutical substance [2].

The method is fully validated according to the European [3] and U.S. [4] regulatory guidelines. It is ideally suited for bioequivalence studies in humans after the administration capecitabine tablets, especially when using a large number of samples [5].

Capecitabine was synthesized in the Chemistry Department and Minisynthesis Department than certified in the R&D Analytical Chemistry Department of the Pharmaceutical Research Institute.

The study was supported by the National Centre for Research and Development of the Republic of Poland under the project No. KB/151/13364/ITI-B/U/08.

[1]    Zufia L., Aldaz A., Giraldez J.: Simple determination of capecytabine and its metabolites by liquid chromatography with ultraviolet detection in single injection. Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Science. 2004; 809 (1): 51-58.

[2]   Łaszcz M., Trzcińska K., Filip K., Szyprowska A., Mucha M., Krzeczyński P.: Stability studies of capecitabine. Journal of Thermal Analysis Calorimetry 2011; 105 (3): 1015-1021.

[3]  Guideline on bioanalytical method validation. European Medicines Agency (EMEA/CHMP/EWP/192217/2009). London, 21 July 2011.

[4]  Guidance for Industry. Bioanalytical Method Validation. U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Center for Veterinary Medicine (CVM). May 2001.

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