Fluorouracil in the environment: analysis, occurrence, degradation and transformation

J Chromatogr A. 2013 May 17;1290:62-72. doi: 10.1016/j.chroma.2013.03.046. Epub 2013 Mar 25.

Abstract

5-Fluorouracil (5-FU) is a fluorinated pyrimidine analogue important in the treatment of cancer whose fate in the environment is yet to be fully addressed. Due to its high polarity 5-FU requires challenging sample preparation and therefore we thoroughly investigated different solid phase extraction mechanisms (ion pair, ion exchange, reversed phase), sorbents and derivatisation agents to enable trace-level analysis of 5-FU based on GC-MS/MS in natural and wastewaters. Ion pair and ion exchange retention mechanisms enable the extraction of 5-FU from deionised water, but were inappropriate for complex environmental matrices, where the reversed phase sorbent Isolute ENV+ gave the best extraction efficiencies (53% and 93% for wastewaters and surface waters, respectively). Further, alkylation was rejected in favour of silylation with MTBSTFA. The achieved limits of quantification (LOQ) for waste and surface waters were 1.6 ng/L and 0.54 ng/L, respectively. The method was used to analyse samples of hospital, wastewater treatment plant influent and effluent and surface waters. 5-FU was quantified in four out of the twelve samples of oncological ward wastewaters and municipal wastewater treatment plant influents in concentrations from 4.7 ng/L to 92 ng/L. This work is also the first to study the environmental transformation of 5-FU and its prodrug capecitabine (CAP). Their removal and transformation was simulated using a series of biodegradation and photodegradation experiments, where 5-FU proved more degradable in comparison to CAP. Transformation of 5-FU and CAP was studied by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QqTOF). Overall, six transformation products for 5-FU and ten for CAP are proposed; 13 of these are to our knowledge published for the first time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotransformation
  • Capecitabine
  • Chromatography, High Pressure Liquid / methods
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / analysis
  • Deoxycytidine / chemistry
  • Environmental Monitoring / methods*
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / analysis*
  • Fluorouracil / chemistry
  • Photolysis
  • Reproducibility of Results
  • Solid Phase Extraction
  • Tandem Mass Spectrometry / methods
  • Waste Water / chemistry*
  • Water Pollutants, Chemical / analysis*

Substances

  • Waste Water
  • Water Pollutants, Chemical
  • Deoxycytidine
  • Capecitabine
  • Fluorouracil