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

•Ion pair solid phase extraction enhances retention of 5-fluorouracil on reversed phase sorbents.•5-Fluorouracil was determined in oncological wastewaters and wastewater treatment plant influents.•5-Fluorouracil is more prone to environmental degradation in comparison to its prodrug capecitabine.•5-Fluorouracil is formed by UV degradation and by microbial biodegradation of capecitabine.•Six transformation products of 5-fluorouracil and ten transformation products of capecitabine are proposed. 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 1.6ng/L and 0.54ng/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 4.7ng/L to 92ng/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.