title: Occurrence of cyclophosphamide and epirubicin in wastewaters by direct injection analysis-liquid chromatography-high-resolution mass spectrometry.
abstract: OBJECTIVE
  According to the high incidence of cancer worldwide, the amount of cytostatic drugs administered to patients has increased. These compounds are excreted to wastewaters, and therefore become potential water contaminants. At this stage, very little is known on the presence and elimination of cytostatic compounds in wastewater treatment plants (WWTP). The aim of this study was to develop a liquid chromatography-high-resolution mass spectrometry (LC-Orbitrap-MS) method for the determination of cyclophosphamide and epirubicin in wastewaters. These compounds represent two outmost used cytostatic agents.
  
  
  METHODS
  Extraction and analytical conditions were optimized for cyclophosphamide and epirubicin in wastewater. Both solid-phase extraction using Oasis 200 mg hydrophilic-lipophilic balanced (HLB) cartridges and direct injection analysis were evaluated. Mass spectral characterization and fragmentation conditions were optimized at 50,000 resolving power (full width at half maximum, m/z 200) to obtain maximum sensitivity and identification performance. Quality parameters (recoveries, limits of detection, and repetitivity) of the methods developed were determined, and best performance was obtained with direct water analysis of the centrifuged wastewater. Finally, this method was applied to determine the presence of cyclophosphamide and epirubicin in wastewaters from a hospital effluent, an urban effluent, and influents and effluents from three WWTP.
  
  
  CONCLUSIONS
  Cyclophosphamide and epirubicin were recovered after 50 mL preconcentration on solid-phase extraction 200 mg Oasis HLB cartridges (87% and 37%, respectively), and no breakthrough was observed by extracting 500 mL of water. Limits of detection were of 0.35 and 2.77 ng/L for cyclophosphamide and epirubicin, respectively. On the other hand, direct injection of water spiked at 1 μg/L provided recoveries of 107% for cyclophosphamide and 44% for epirubicin and limits of detection from 3.1 to 85 ng L(-1), respectively. The analysis of wastewaters using direct injection analysis revealed the presence of cyclophosphamide and epirubicin in WWTP influents and hospital and urban effluents at levels ranging from 5.73 to 24.8 μg L(-1).
  
  
  CONCLUSIONS
  The results obtained in this study demonstrate the capability of LC-Orbitrap-MS for accurate trace analysis of these very polar contaminants. This method permitted to identify cyclophosphamide and epirubicin in wastewaters and influents of WWTP, but no traces were detected in WWTP effluents. The methodology herein developed is sensitive and robust and applicable for screening of a large number of samples since no preconcentration is needed.
authors.affiliation: Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18-26, 08034 Barcelona, Catalonia, Spain.
authors.forename: Cristian
authors.initials: C
authors.lastname: Gómez-Canela
authors.forename: Nuria
authors.initials: N
authors.lastname: Cortés-Francisco
authors.forename: Xavier
authors.initials: X
authors.lastname: Oliva
authors.forename: Cristina
authors.initials: C
authors.lastname: Pujol
authors.forename: Francesc
authors.initials: F
authors.lastname: Ventura
authors.forename: Silvia
authors.initials: S
authors.lastname: Lacorte
authors.forename: Josep
authors.initials: J
authors.lastname: Caixach
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis*; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D003520:Cyclophosphamide / Q000032:analysis*; D015251:Epirubicin / Q000032:analysis*; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D052616:Solid Phase Extraction / Q000295:instrumentation / Q000379:methods; D014865:Waste Disposal, Fluid / Q000295:instrumentation / Q000379:methods; D014874:Water Pollutants, Chemical / Q000032:analysis*
chemical_list: D000970:Antineoplastic Agents; D014874:Water Pollutants, Chemical; D015251:Epirubicin; D003520:Cyclophosphamide