Simple determination of capecitabine and its metabolites by liquid chromatography with ultraviolet detection in a single injection
Zufía L, Aldaz A [SP], Giráldez J.
Pharmacy Department, University Hospital of Navarra, c/Pío XII s/n, 31008 Pamplona, Spain.
Magazine: Journal of Chromatography
Date: Sep 1, 2004Pharmacy [SP]
Capecitabine (N4-pentoxycarbonyl-5'-deoxy-5-fluorocytidine, Xeloda), a prodrug of 5-fluorouracil (5-FU), is an oral tumor-selective fluoropyrimidine carbamate approved in the treatment of colorectal and breast cancer. It has a preferential activation to 5-FU by thymidine phosphorilase (TP) in target tumor tissues through a series of three metabolic steps minimizing the exposure of normal tissues to 5-FU. It offers the potential of less gastrointestinal toxicity and advantages in terms of convenience and quality of life for the patient, in addition to cost-effectiveness as compared with intravenous 5-FU chemotherapy.
We developed a high performance liquid chromatography assay for the determination of plasma capecitabine and its nucleoside metabolite concentrations and 5-FU catabolite dihydro-5-fluorouracil in a single step extraction and a single HPLC injection. The retention times of dihydro-5-fluorouracil, 5-FU, 5'-deoxy-5-fluorouridine (5'-DFUR) and capecitabine were 3.6, 4.4, 11.4 and 20.4 min, respectively and the internal standard retention times were 8.7 and 12.2 min for 5-bromouracil (5-BU) and tegafur, respectively. The limit of detection was 0.01 microg/ml for capecitabine and its nucleoside metabolites and the limit of quantification was 0.025 microg/ml. Extraction efficiency was >80% with a single solvent mixture extraction step for all analytes of interest. The assay had good precision, the within-day and between-day standard deviation of the mean (R.S.D.) being <10% in the linear range 0.025-10 microg/ml.
The authors conclude that the method described here is ideally suited for the therapeutic monitoring of capecitabine and its metabolites.
CITATION J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Sep 25;809(1):51-8
you maybe interested
The Clínica is the greater private hospital with technological equipment of Spain, all in a single center.
The professionals of the Clínica perform continuous research and training, always to the benefit of the patient.
Learn why we are different from other healthcare centers. Quality, speed, comfort and results.