Simple determination of capecitabine and its metabolites by liquid chromatography with ultraviolet detection in a single injection.
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.
Zufía
L
L
Pharmacy Department, University Hospital of Navarra, c/Pío XII s/n, 31008 Pamplona, Spain. lzufia@unav.es
Aldaz
A
A
Giráldez
J
J
D000964:Antimetabolites, Antineoplastic / Q000097:blood*; D000069287:Capecitabine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000097:blood*; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D011355:Prodrugs / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil