Zanamivir (Za) is a highly polar and hydrophilic antiviral drug used for the treatment of influenza A viruses. Za has been detected in rivers of Japan and it's environmental occurrence has the risk of inducing antiviral resistant avian influenza viruses. In this study, a rapid automated online solid phase extraction liquid chromatography method using bonded zwitterionic stationary phases and tandem mass spectrometry (SPE/LC-MS/MS) for trace analysis of Za was developed. Furthermore, an internal standard (IS) calibration method capable of quantifying Za in Milli-Q, surface water, sewage effluent and sewage influent was evaluated. Optimum pre-extraction sample composition was found to be 95/5 v/v acetonitrile/water sample and 1% formic acid. The developed method showed acceptable linearities (r(2)≥0.994), filtration recovery (≥91%), and intra-day precisions (RSD≤16%), and acceptable and environmentally relevant LOQs (≤20ngL(-1)). Storage tests showed no significant losses of Za during 20 days and +4/-20°C (≤12%) with the exception of influent samples, which should be kept at -20°C to avoid significant Za losses. The applicability of the method was demonstrated in a study on phototransformation of Za in unfiltered and filtered surface water during 28 days of artificial UV irradiation exposure. No significant (≤12%) phototransformation was found in surface water after 28 days suggesting a relatively high photostability of Za and that Za should be of environmental concern.

Cracow University of Technology Faculty of Engineering and Chemical Technology Warszawska 24 Strasse 31 155 Cracow Poland

Department of Chemistry Umeå University 901 87 Umeå Sweden

Department of Chemistry Umeå University 901 87 Umeå Sweden; University of South Bohemia in Ceske Budejovice Faculty of Fisheries and Protection of Waters South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses Zatisi 728 2 389 25 Vodnany Czech Republic

Merck Millipore Frosundaviks Alle 1 SE 16970 Stockholm Sweden

Section for Infectious Diseases Department of Medical Sciences Uppsala University Sweden; Zoonotic Science Center Department of Medical Biochemistry and Microbiology Uppsala University Uppsala Sweden

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