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Environmental problems - Chemical approaches
RESEARCH ARTICLE

UV-induced photodegradation of oseltamivir (Tamiflu) in water

Alfred Y. C. Tong A B E , Rhiannon Braund B , Eng W. Tan A , Louis A. Tremblay C , Tristan Stringer D , Katherine Trought D and Barrie M. Peake A E
+ Author Affiliations
- Author Affiliations

A Chemistry Department, University of Otago, PO Box 56, Dunedin 9054, New Zealand.

B New Zealand National School of Pharmacy, University of Otago, PO Box 56, Dunedin 9054, New Zealand.

C Cawthron Institute, Private Bag 2, Nelson, New Zealand.

D Landcare Research, PO Box 40, Lincoln 7640, New Zealand.

E Corresponding authors. Email: alfred.tong@otago.ac.nz; bpeake@chemistry.otago.ac.nz

Environmental Chemistry 8(2) 182-189 https://doi.org/10.1071/EN10095
Submitted: 24 August 2010  Accepted: 7 February 2011   Published: 2 May 2011

Environmental context. Oseltamivir (Tamiflu) is widely used to prevent and treat influenza but conventional wastewater processes involving sedimentation and biotic oxidation do not appear to significantly remove it from sewage, leading to its discharge into the environment. A range of advanced oxidation processes (AOPs) involving photolysis of aqueous solutions of oseltamivir with UV alone, UV/H2O2 and UV/H2O2/FeII is demonstrated to lead to photodegradation of oseltamivir to products with no ecotoxicity observed. These AOPs may therefore offer potentially environmentally friendly sewage water treatment options.

Abstract. Aqueous solutions of the antiviral drug oseltamivir phosphate (OSP, Tamiflu, (3R,4R,5S)-ethyl 4-acetamido-5-amino-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate) were degraded using advanced oxidation processes (AOPs) involving photodegradation with UV alone, UV/H2O2 and UV/H2O2/FeII (photo-Fenton reaction). The photodecay of the parent OSP in all three cases followed first-order kinetics with respective rate constants of 0.21, 1.56 and 1.75 min–1 at 20°C in pH 7 phosphate-buffered Milli-Q water. The rate of UV/H2O2 photolysis in the presence of 2-methylpropan-2-ol was significantly slower with an approximate first-order rate constant of 0.13 min–1 suggesting the involvement of OH in the degradation process. NMR spectroscopy, mass spectrometry and high-performance liquid chromatography (HPLC) with UV diode array detection were used to identify the crude photoproduct as the hydroxylated OSP derivative (3S,4R,5S)-ethyl 4-acetamido-5-amino-2-hydroxy-3-(pentan-3-yloxy)cyclohexanecarboxylate that occurs by an unknown mechanism. OSP and this crude photoproduct demonstrated no effect on the survival of Quinquelaophonte sp. over 96 h.

Additional keywords: advanced oxidation process, antivirals, ecotoxicity, pharmaceuticals.


References

[1]  W. B. Dreitlein, J. Maratos, J. Brocavich, Zanamivir and oseltamivir: two new options for the treatment and prevention of influenza. Clin. Therapeut. 2001, 23, 327.
Zanamivir and oseltamivir: two new options for the treatment and prevention of influenza.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjvVartr4%3D&md5=2580b0909acec6443e6d9eb5120a3f88CAS |

[2]  I. R. McNicholl, J. J. McNicholl, Neuraminidase inhibitors: zanamivir and oseltamivir. Ann. Pharmacother. 2001, 35, 57.
Neuraminidase inhibitors: zanamivir and oseltamivir.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXoslCgsA%3D%3D&md5=e28c1ca4efcc54335a9159755d5b1608CAS | 11197587PubMed |

[3]  R. Dutkowski, B. Thakrar, E. Froehlich, P. Suter, C. Oo, P. Ward, Safety and pharmacology of oseltamivir in clinical use. Drug Saf. 2003, 26, 787.
Safety and pharmacology of oseltamivir in clinical use.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXnslGmtrw%3D&md5=33028cc25d66a5fe34052ddba5d69c73CAS | 12908848PubMed |

[4]  A. C. Singer, M. A. Nunn, E. A. Gould, A. C. Johnson, Potential risks associated with the proposed widespread use of Tamiflu. Environ. Health Perspect. 2007, 115, 102.[Published online ahead of print 11 October 2006]
Potential risks associated with the proposed widespread use of Tamiflu.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVOlur0%3D&md5=aa13f839ae82c6845e063b40ef334749CAS | 17366827PubMed |

[5]  T. Tillett, A measure of resistance detecting Tamiflu metabolite in sewage discharge and river water. Environ. Health Perspect. 2010, 118, A34..
| 20061221PubMed |

[6]  H. Söderström, J. D. Järhult, B. Olsen, R. Lindberg, H. Tanaka, J. Fick, Detection of the antiviral drug oseltamivir in aquatic environments. PLoS ONE 2009, 4, e6064.
Detection of the antiviral drug oseltamivir in aquatic environments.Crossref | GoogleScholarGoogle Scholar | 19557131PubMed |

[7]  M. L. Saccà, C. Accinelli, J. Fick, R. Lindberg, B. Olsen, Environmental fate of the antiviral drug Tamiflu in two aquatic ecosystems. Chemosphere 2009, 75, 28.
Environmental fate of the antiviral drug Tamiflu in two aquatic ecosystems.Crossref | GoogleScholarGoogle Scholar | 19124147PubMed |

[8]  J. Fick, R. H. Lindberg, M. Tysklind, P. D. Haemig, J. Waldenstrom, A. Wallensten, B. Olsen, Antiviral oseltamivir is not removed or degraded in normal sewage water treatment: implications for development of resistance by Influenza A virus. PLoS ONE 2007, 2, e986.
Antiviral oseltamivir is not removed or degraded in normal sewage water treatment: implications for development of resistance by Influenza A virus.Crossref | GoogleScholarGoogle Scholar | 17912363PubMed |

[9]  J. B. Ellis, Antiviral pandemic risk assessment for urban receiving waters. Water Sci. Technol. 2010, 61, 879.
Antiviral pandemic risk assessment for urban receiving waters.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXkvVOhur8%3D&md5=6875da44e09d347f2873906b787b1737CAS | 20182065PubMed |

[10]  G. C. Ghosh, N. Nakada, N. Yamashita, H. Tanaka, Oseltamivir carboxylate, the active metabolite of oseltamivir phosphate (Tamiflu), detected in sewage discharge and river water in Japan. Environ. Health Perspect. 2010, 118, 103..
| 20056566PubMed |

[11]  C. Prasse, M. P. Schlusener, R. Schulz, T. A. Ternes, Antiviral drugs in wastewater and surface waters: a new pharmaceutical class of environmental relevance? Environ. Sci. Technol. 2010, 44, 1728.
Antiviral drugs in wastewater and surface waters: a new pharmaceutical class of environmental relevance?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXht1Sgsb0%3D&md5=df9ea0889e5d472acda8e9f5b6538f90CAS | 20108960PubMed |

[12]  P. Bartels, W. von Tumpling, The environmental fate of the antiviral drug oseltamivir carboxylate in different waters. Sci. Total Environ. 2008, 405, 215.
The environmental fate of the antiviral drug oseltamivir carboxylate in different waters.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtFOjurnJ&md5=1c33a8bf4f5ec62f5ab6ad0893335885CAS | 18675443PubMed |

[13]  C. Accinelli, A. Barra Carracciolo, P. Grenni, M. L. Sacca, Degradation of the antiviral drug oseltamivir (Tamiflu) in surface water samples. Int. J. Environ. Anal. Chem. 2007, 87, 579.
Degradation of the antiviral drug oseltamivir (Tamiflu) in surface water samples.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXlvFejurw%3D&md5=cc2c6beffece8d288aed6bf0fe8c103aCAS |

[14]  C. Accinelli, M. L. Sacca, I. Batisson, J. Fick, M. Mencarelli, R. Grabic, Removal of oseltamivir (Tamiflu) and other selected pharmaceuticals from wastewater using a granular bioplastic formulation entrapping propagules of Phanerochaete chrysosporium. Chemosphere 2010, 81, 436.
Removal of oseltamivir (Tamiflu) and other selected pharmaceuticals from wastewater using a granular bioplastic formulation entrapping propagules of Phanerochaete chrysosporium.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFGjsLjM&md5=aefb22bfc3b7409d24a6d4f62f078c3dCAS | 20673959PubMed |

[15]  C. Accinelli, M. L. Sacca, J. Fick, M. Mencarelli, M. J. Lindberg, B. Olsen, Dissipation and removal of oseltamivir (Tamiflu) in different aquatic environments. Chemosphere 2010, 79, 891.
Dissipation and removal of oseltamivir (Tamiflu) in different aquatic environments.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXkvFCrs78%3D&md5=a7e2376b5a047c9eba4a66e10ca00930CAS | 20226496PubMed |

[16]  J. O. Straub, An environmental risk assessment for oseltamivir (Tamiflu®) for sewage works and surface waters under seasonal-influenza and pandemic use conditions. Ecotoxicol. Environ. Saf. 2009, 72, 1625.
An environmental risk assessment for oseltamivir (Tamiflu®) for sewage works and surface waters under seasonal-influenza and pandemic use conditions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtVSmsbnN&md5=28b40616289b4aa1746e0af7d0568891CAS | 19560203PubMed |

[17]  A. C. Singer, B. M. Howard, A. C. Johnson, C. J. Knowles, S. Jackman, C. Accinelli, A. B. Caracciolo, I. Bernard, S. Bird, T. Boucard, A. Boxall, J. V. Brian, E. Cartmell, C. Chubb, J. Churchley, S. Costigan, M. Crane, M. J. Dempsey, B. Dorrington, B. Ellor, J. Fick, J. Holmes, T. Hutchinson, F. Karcher, S. L. Kelleher, P. Marsden, G. Noone, M. A. Nunn, J. Oxford, T. Rachwal, N. Roberts, M. Roberts, M. L. Sacca, M. Sanders, J. O. Straub, A. Terry, D. Thomas, S. Toovey, R. Townsend, N. Voulvoulis, C. Watts, Meeting report: Risk assessment of Tamiflu use under pandemic conditions. Environ. Health Perspect. 2008, 116, 1563.
Meeting report: Risk assessment of Tamiflu use under pandemic conditions.Crossref | GoogleScholarGoogle Scholar | 19057712PubMed |

[18]  A. C. Singer, M. A. Nunn, E. A. Gould, A. C. Johnson, Potential risks associated with the proposed widespread use of Tamiflu. Environ. Health Perspect. 2007, 115, 102. [Published online ahead of print 11 October 2006]10.1289/EHP.9574

[19]  T. H. Hutchinson, A. Beesley, P. E. Frickers, J. W. Readman, J. P. Shaw, J. O. Straub, Extending the environmental risk assessment for oseltamivir (Tamiflu) under pandemic use conditions to the coastal marine compartment. Environ. Int. 2009, 35, 931.
Extending the environmental risk assessment for oseltamivir (Tamiflu) under pandemic use conditions to the coastal marine compartment.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXms1yisr8%3D&md5=72576e94f6a25fab882e2bd544ba0151CAS | 19395032PubMed |

[20]  B. I. Escher, N. Bramaz, J. Lienert, J. Neuwoehner, J. O. Straub, Mixture toxicity of the antiviral drug Tamiflu® (oseltamivir ethylester) and its active metabolite oseltamivir acid. Aquat. Toxicol. 2010, 96, 194.
Mixture toxicity of the antiviral drug Tamiflu® (oseltamivir ethylester) and its active metabolite oseltamivir acid.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlWktrY%3D&md5=a93ad2b71efc11f01baa398ea9924e30CAS | 19939473PubMed |

[21]  M. Andrawiss, Flu pills for a pandemic threat. Drug Discov. Today 2005, 10, 811.
Flu pills for a pandemic threat.Crossref | GoogleScholarGoogle Scholar | 15970260PubMed |

[22]  D. Reddy, Responding to pandemic (H1N1) 2009 influenza: the role of oseltamivir. J. Antimicrob. Chemother. 2010, 65, ii35.
Responding to pandemic (H1N1) 2009 influenza: the role of oseltamivir.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXjt1KqtLw%3D&md5=96d6acf92c433bb2463e066164cea26cCAS | 20215134PubMed |

[23]  S. A. S. Melo, A. G. Trovo, I. R. Bautitz, R. F. P. Nogueira, Degradation of residual pharmaceuticals by advanced oxidation processes. Quim. Nova 2009, 32, 188..

[24]  F. L. Rosario-Ortiz, E. C. Wert, S. A. Snyder, Evaluation of UV/H2O2 treatment for the oxidation of pharmaceuticals in wastewater. Water Res. 2010, 44, 1440.
Evaluation of UV/H2O2 treatment for the oxidation of pharmaceuticals in wastewater.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXitFykt78%3D&md5=a7bcbd0e675e42d3ae271353c35bfccbCAS | 19931113PubMed |

[25]  R. Andreozzi, V. Caprio, R. Marotta, D. Vogna, Paracetamol oxidation from aqueous solutions by means of ozonation and H2O2/UV system. Water Res. 2003, 37, 993.
Paracetamol oxidation from aqueous solutions by means of ozonation and H2O2/UV system.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXmtVartg%3D%3D&md5=ebe581a8c62388ac887af5ac331015e3CAS | 12553974PubMed |

[26]  F. Yuan, C. Hu, X. Hu, J. Qu, M. Yang, Degradation of selected pharmaceuticals in aqueous solution with UV and UV/H2O2. Water Res. 2009, 43, 1766.
Degradation of selected pharmaceuticals in aqueous solution with UV and UV/H2O2.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjsVequro%3D&md5=528cd5aecc2b9c0d8435c9cb49a546e0CAS | 19232423PubMed |

[27]  A. G. Trovó, S. A. S. Melo, R. F. P. Nogueira, Photodegradation of the pharmaceuticals amoxicillin, bezafibrate and paracetamol by the photo-Fenton process – application to sewage treatment plant effluent. J. Photochem. Photobiol. Chem. 2008, 198, 215.
Photodegradation of the pharmaceuticals amoxicillin, bezafibrate and paracetamol by the photo-Fenton process – application to sewage treatment plant effluent.Crossref | GoogleScholarGoogle Scholar |

[28]  E. Fisher, Ferrioxalate actinometry. European Photochemistry Association Newsletter 1984, 21, 33..

[29]  M. Vonpiechowski, M. A. Thelen, J. Hoigne, R. E. Buhler, Tert-butanol as an OH-scavenger in the pulse-radiolysis of oxygenated aqueous systems. Ber. Bunsen. Phys. Chem. 1992, 96, 1448..

[30]  H. Zhang, F. Liu, X. Wu, J. Zhang, D. Zhang, Degradation of tetracycline in aqueous medium by electrochemical method. Asia-Pac. J. Chem. Eng. 2009, 4, 568.
Degradation of tetracycline in aqueous medium by electrochemical method.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtlegtrbN&md5=bf4bcb9c18d253fd52087da8a331b036CAS |

[31]  I. Kim, N. Yamashita, H. Tanaka, Photodegradation of pharmaceuticals and personal care products during UV and UV/H2O2 treatments. Chemosphere 2009, 77, 518.
Photodegradation of pharmaceuticals and personal care products during UV and UV/H2O2 treatments.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtF2htLjJ&md5=219b4442cc7d561a641dd2047d1cba36CAS | 19712957PubMed |

[32]  F. J. Real, J. L. Acero, F. J. Benitez, G. Roldan, L. C. Fernandez, Oxidation of hydrochlorothiazide by UV radiation, hydroxyl radicals and ozone: Kinetics and elimination from water systems. Chem. Eng. J. 2010, 160, 72.
Oxidation of hydrochlorothiazide by UV radiation, hydroxyl radicals and ozone: Kinetics and elimination from water systems.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlt1Smu7o%3D&md5=7d298be8ea54a5612f649168c3448d09CAS |

[33]  W. Z. Li, S. G. Lu, Z. F. Qiu, K. F. Lin, Clofibric acid degradation in UV254/H2O2 process: Effect of temperature. J. Hazard. Mater. 2010, 176, 1051.
Clofibric acid degradation in UV254/H2O2 process: Effect of temperature.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXpsVeltg%3D%3D&md5=dbfbfb63bcaeaafbee4a91e2ac897c93CAS | 20042284PubMed |

[34]  M. DellaGreca, A. Fiorentino, M. Isidori, M. Lavorgna, L. Previtera, M. Rubino, F. Temussi, Toxicity of prednisolone, dexamethasone and their photochemical derivatives on aquatic organisms. Chemosphere 2004, 54, 629.
Toxicity of prednisolone, dexamethasone and their photochemical derivatives on aquatic organisms.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXos1Ogtbc%3D&md5=5db3a405d088bd7dd59a23bee6042ce0CAS | 14599508PubMed |

[35]  S. Raisuddin, K. W. H. Kwok, K. M. Y. Leung, D. Schlenk, J.-S. Lee, The copepod Tigriopus: a promising marine model organism for ecotoxicology and environmental genomics. Aquat. Toxicol. 2007, 83, 161.
The copepod Tigriopus: a promising marine model organism for ecotoxicology and environmental genomics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXntFKjtLc%3D&md5=608abc8b5c5988a0db0d398906121d39CAS | 17560667PubMed |

[36]  D. Greenstein, S. Bay, B. Anderson, G. T. Chandler, J. D. Farrar, C. Keppler, B. Phillips, A. Ringwood, D. Young, Comparison of methods for evaluating acute and toxicity in marine sediments. Environ. Toxicol. Chem. 2008, 27, 933.
Comparison of methods for evaluating acute and toxicity in marine sediments.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXktFGntbk%3D&md5=25683a92a810b9952753b82e93351ec2CAS | 18333680PubMed |