Simple determination of capecitabine and its metabolites by liquid chromatography with ultraviolet detection in a single injection
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- 作者：Zufí ; a ; L. ; Aldaz ; A. ; Girá ; ldez ; J.
- 关键词：Capecitabine ; 5-Fluorouracil ; Dihydro-5-fluorouracil
- 刊名：Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences
- 出版年：2004
- 出版时间：September 25, 2004
- 年：2004
- 卷：809
- 期：1
- 页码：51-58
- 全文大小：120 K
文摘
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 20.4min, respectively and the internal standard retention times were 8.7 and 12.2min for 5-bromouracil (5-BU) and tegafur, respectively. The limit of detection was 0.01μg/ml for capecitabine and its nucleoside metabolites and the limit of quantification was 0.025μg/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 0.025–10μg/ml. The authors conclude that the method described here is ideally suited for the therapeutic monitoring of capecitabine and its metabolites.