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

Abstract

Summary:

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 β-hydroxyethyltheophylline, respectively. The limit of quantification was 0.0125 μg/mL for 5-FU and 0.05 μg/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 μg/mL) and tegafur (0.5–150 μg/mL) was always <8%. The authors conclude that the method described here is ideally suited for the therapeutic monitoring of 5-FU and tegafur.