title: Oseltamivir carboxylate, the active metabolite of oseltamivir phosphate (Tamiflu), detected in sewage discharge and river water in Japan.
abstract: BACKGROUND
  Oseltamivir phosphate (OP; Tamiflu) is a prodrug of the anti-influenza neuraminidase inhibitor oseltamivir carboxylate (OC) and has been developed for the treatment and prevention of both A and B strains of influenza. The recent increase in OP resistance in influenza A virus (H1N1; commonly called "swine flu") has raised questions about the widespread use of Tamiflu in seasonal epidemics and the potential ecotoxicologic risk associated with its use in the event of a pandemic.
  
  
  OBJECTIVE
  The objectives of this study were to develop an analytical method for quantitative determination of OC in sewage treatment plant (STP) effluent and receiving river water, and to investigate the occurrence of OC in STP effluent and river water in Japan during a seasonal flu outbreak.
  
  
  METHODS
  We developed an analytical method based on solid-phase extraction followed by liquid chromatography-tandem mass spectrometry. Using this method, we analyzed samples from three sampling campaigns conducted during the 2008-2009 flu season in Kyoto City, Japan.
  
  
  RESULTS
  The highest concentration of OC detected in STP discharge was 293.3 ng/L from a conventional activated-sludge-based STP; however, we detected only 37.9 ng/L from an advanced STP with ozonation as a tertiary treatment. In the receiving river water samples, we detected 6.6-190.2 ng/L OC, during the peak of the flu season.
  
  
  CONCLUSIONS
  OC is present in STP effluent and river water only during the flu season. Ozonation as tertiary treatment in STP will substantially reduce the OC load in STP effluent during an influenza epidemic or pandemic.
authors.affiliation: Research Centre for Environmental Quality Management, Graduate School of Engineering, Kyoto University, Otsu, Shiga, Japan. gopal@biwa.eqc.kyoto-u.ac.jp
authors.forename: Gopal C
authors.initials: GC
authors.lastname: Ghosh
authors.forename: Norihide
authors.initials: N
authors.lastname: Nakada
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamashita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000998:Antiviral Agents / Q000032:analysis; D002853:Chromatography, Liquid / Q000379:methods; D004350:Drug Residues / Q000009:adverse effects / Q000032:analysis*; D024882:Drug Resistance, Viral; D004782:Environmental Health; D004784:Environmental Monitoring; D005618:Fresh Water / Q000032:analysis; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy; D007564:Japan; D009975:Orthomyxoviridae / Q000187:drug effects; D053139:Oseltamivir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000032:analysis* / Q000378:metabolism; D045483:Rivers / Q000737:chemistry*; D012621:Seasons; D012722:Sewage / Q000009:adverse effects / Q000032:analysis*; D053719:Tandem Mass Spectrometry / Q000379:methods; D014874:Water Pollutants, Chemical / Q000009:adverse effects / Q000032:analysis*; D018508:Water Purification
chemical_list: D000998:Antiviral Agents; D012722:Sewage; D014874:Water Pollutants, Chemical; D053139:Oseltamivir; C535162:oseltamivir carboxylate