1-(tetrahydro-2-furanyl)-5-fluorouracil (Ftorafur) determined in rat hair as an index of drug exposure

Abstract

The fluorescence derivatization of 1-(tetrahydro-2-furanyl)-5-fiuorouracil (Ftorafur, FT) with 4-bromomethyl-6, 7-dimethoxycoumarin (BrMdmc) with 18-crown-6 as catalyst was utilized for a sensitive and selective liquid chromatographic method to determine the concentration of FT in hair. Hair samples collected from rats, which had received FT intraperitoneally for 1 to 4 weeks, were dissolved in 1 M NaOH by heating at 80 °C for 30 min. A three-step extraction procedure for FT in the dissolved hair was used before and after the derivatization of FT with BrMdmc. The detection limit achieved was <0.16 ng/mg hair. A dose-dependent accumulation of FT was evident in the rat hair (r = 0.914, p < 0.001): 0.24 ± 0.07, 1.35 ± 0.39, and 2.85 ± 0.74 ng/mg hair (mean ± SD, n = 4–5) at the doses of 5, 15, and 50 mg/kg/day for 4 weeks, respectively. In the rats that had received the highest dose of FT, the accumulation of FT in the hair depended also on the duration of FT administration: 0.82 ± 0.33 (1 week), 1.52 ± 0.38 (2 weeks), and 2.85 ± 0.74 (4 weeks) ng/mg hair (n = 4–5). These findings suggest that the analysis of an oral antineoplasmic FT in the hair may be useful for assessing the degree of exposure to the drug.