Determination of 5-fluorouracil and tegafur in tear fluid of patients treated with oral fluoropyrimidine anticancer agent, S-1

Jpn J Ophthalmol. 2018 Jul;62(4):432-437. doi: 10.1007/s10384-018-0603-8. Epub 2018 Jun 21.

Abstract

Purpose: To establish a method for the measurement of 5-fluorouracil (5-FU), and tegafur (FT) in tear samples from patients treated with oral fluoropyrimidine anticancer agent S-1.

Study design: Cross-sectional study.

Methods: High performance liquid chromatographic (HPLC) method reported for plasma samples was modified for tear samples. Simulated-tear solutions containing lactoferrin, lysozyme and standard solution containing 5-FU or FT were prepared for preliminary measurements. Tear samples from seven patients treated with S-1 were included. The tears were collected following S-1 administration using Schirmer's strips.

Results: 5-FU and FT concentrations of pure standard solution without extraction process were detected as original concentration. However, on extraction, FT samples in simulated-tear solution showed a peak for 5-FU but not for FT. FT was converted to 5-FU in the extraction process. Decomposition from FT to 5-FU was suppressed when 50 mg/mL bovine serum albumin was added during extraction. The mean concentrations of 5-FU and FT in tears during S-1 treatment were 0.17 ± 0.11 and 1.94 ± 0.71 μg/mL, respectively.

Conclusion: A simple HPLC method to determine 5-FU and FT in tear samples was established.

Keywords: 5-fluorouracil; Cornea; High performance liquid chromatography; S-1; Tears.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage
  • Chromatography, High Pressure Liquid
  • Cross-Sectional Studies
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Fluorouracil / pharmacokinetics*
  • Humans
  • Immunosuppressive Agents / pharmacokinetics
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Oxonic Acid / administration & dosage*
  • Tears / chemistry*
  • Tegafur / administration & dosage
  • Tegafur / pharmacokinetics*

Substances

  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • Immunosuppressive Agents
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Fluorouracil