title: Fluorouracil in the environment: analysis, occurrence, degradation and transformation.
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.
authors.affiliation: Jožef Stefan Institute, Jamova 39, Ljubljana, Slovenia. tina.kosjek@ijs.si
authors.forename: Tina
authors.initials: T
authors.lastname: Kosjek
authors.forename: Silva
authors.initials: S
authors.lastname: Perko
authors.forename: Dušan
authors.initials: D
authors.lastname: Žigon
authors.forename: Ester
authors.initials: E
authors.lastname: Heath
mesh_terms: D001711:Biotransformation; D000069287:Capecitabine; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry; D004784:Environmental Monitoring / Q000379:methods*; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000032:analysis* / Q000737:chemistry; D010782:Photolysis; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000379:methods; D062065:Wastewater / Q000737:chemistry*; D014874:Water Pollutants, Chemical / Q000032:analysis*
chemical_list: D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D062065:Wastewater; D014874:Water Pollutants, Chemical