Determination of 5-fluorouracil and its prodrug tegafur in plasma and tissue by high-performance liquid chromatography in a single injection: validation for application in clinical pharmacokinetic studies.
Tegafur, a prodrug of 5-fluorouracil (5-FU), is an oral fluorouracil antitumor drug used for the management of adenocarcinomas. It has an efficacy similar to that of intravenous 5-FU, with potential advantages in terms of convenience and quality of life for the patient and cost-effectiveness as compared with intravenous chemotherapy. The authors developed a high-performance liquid chromatography (HPLC) assay for the determination of tissue or plasma tegafur and 5-FU concentration in a single step extraction and a single HPLC injection. The retention times of 5-FU and tegafur were 5 and 16.5 minutes, respectively, and the internal standard retention times were 11.5 and 17.5 minutes for 5-bromouracil (5-BU) and beta-hydroxyethyltheophylline, respectively. The limit of quantification was 0.0125 microg/mL for 5-FU and 0.05 microg/mL for tegafur. The assay had good recovery (96.5% +/- 9.45% and 97.5% +/- 7.89% for 5-FU in plasma and tissue, respectively, and 88.5% +/- 12.17% and 104.9% +/- 8.77% for tegafur in plasma and tissue, respectively). Precision was good: the within-day and between-day standard deviation of the mean (RSD) for 5-FU (0.0125-5 microg/mL) and tegafur (0.5-150 microg/mL) was always <8%. The authors conclude that the method described here is ideally suited for the therapeutic monitoring of 5-FU and tegafur.
Zufía
Laura
L
Pharmacy Department, University Hospital of Navarra, Pamplona, Spain. lzufia@unav.es
Aldaz
Azucena
A
Castellanos
Carmen
C
Giráldez
Joaquín
J
D000964:Antimetabolites, Antineoplastic / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005472:Fluorouracil / Q000032:analysis* / Q000097:blood; D006801:Humans; D011355:Prodrugs / Q000378:metabolism*; D005641:Tegafur / Q000032:analysis* / Q000097:blood; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D005641:Tegafur; D005472:Fluorouracil