The article evaluated the degradation of the captopril in aqueous solution after ozonation and chlorination. The process was continuously monitored focusing on the identification, mass spectrometry and elucidation of its by-products by applying direct infusion and high performance liquid chromatography, electrospray ionization high resolution mass spectrometry, in the negative ion mode. The cytotoxicity of its by-products solutions were evaluated with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. It was observed through that after 30 min of ozonation and chlorination, there was complete oxidation of captopril, i.e. , 100% removal efficiency. At these conditions, the rate of mineralization, by total organic carbon, was only 7.63% for ozonation and 6.40% for chlorination, evidencing the formation of degradation by-products. Ten captopril by-products were identified and their respective chemical structures elucidations are proposed. The treated samples and their by-products were nontoxic to HepG2 cells by MTT assay.
KeywordsChlorinationOzonationCaptoprilHigh-Resolution Mass SpectrometryLiquid ChromatographyCharacterization of By-ProductsMTT Assay
Serra-Roig, M.P., Jurado, A., Diaz-Cruz, M.S., Vazquez-Sune, E., Pujades, E. and Barcelo, D. (2016) Occurrence, Fate and Risk Assessment of Personal Care Products in River-Groundwater Interface. Science of the Total Environment.
Stumpf, M., Ternes, T.A., Wilken, R.-D., Silvana Vianna, R. and Baumann, W. (1999) Polar Drug Residues in Sewage and Natural Waters in the State of Rio de Janeiro, Brazil. Science of the Total Environment, 225, 135-141. https://doi.org/10.1016/S0048-9697(98)00339-8
Andreozzi, R., Raffaele, M. and Nicklas, P. (2003) Pharmaceuticals in STP Effluents and Their Solar Photodegradation in Aquatic Environment. Chemosphere, 50, 1319-1330. https://doi.org/10.1016/S0045-6535(02)00769-5
Heberer, T. (2002) Occurrence, Fate, and Removal of Pharmaceutical Residues in the Aquatic Environment: A Review of Recent Research Data. Toxicology Letters, 131, 5-17. https://doi.org/10.1016/S0378-4274(02)00041-3
Santiago-Morales, J., Agüera, A., Gómez, M.D.M., Fernández-Alba, A.R., Giménez, J., Esplugas, S. and Rosal, R. (2013) Transformation Products and Reaction Kinetics in Simulated Solar Light Photocatalytic Degradation of Propranolol Using Ce-Doped TiO2. Applied Catalysis B: Environmental, 129, 13-29. https://doi.org/10.1016/j.apcatb.2012.09.023
Bedner, M. and MacCrehan, W.A. (2005) Transformation of Acetaminophen by Chlorination Produces the Toxicants 1,4-Benzoquinone and N-Acetyl-p-benzo-quinone Imine. Environmental Science & Technology, 40, 516-522. https://doi.org/10.1021/es0509073
Acero, J.L., Benitez, F.J., Real, F.J. and Roldan, G. (2010) Kinetics of Aqueous Chlorination of Some Pharmaceuticals and Their Elimination from Water Matrices. Water Research, 44, 4158-4170. https://doi.org/10.1016/j.watres.2010.05.012
von Gunten, U. (2003) Ozonation of Drinking Water: Part I. Oxidation Kinetics and Product Formation. Water Research, 37, 1443-1467. https://doi.org/10.1016/S0043-1354(02)00457-8
von Gunten, U. (2003) Ozonation of Drinking Water: Part II. Disinfection and By-Product Formation in Presence of Bromide, Iodide or Chlorine. Water Research, 37, 1469-1487. https://doi.org/10.1016/S0043-1354(02)00458-X
Broseus, R., Vincent, S., Aboulfadl, K., Daneshvar, A., Sauve, S., Barbeau, B. and Prevost, M. (2009) Ozone Oxidation of Pharmaceuticals, Endocrine Disruptors and Pesticides during Drinking Water Treatment. Water Research, 43, 4707-4717. https://doi.org/10.1016/j.watres.2009.07.031
Lee, Y. and von Gunten, U. (2010) Oxidative Transformation of Micropollutants during Municipal Wastewater Treatment: Comparison of Kinetic Aspects of Selective (Chlorine, Chlorine Dioxide, Ferrate VI, and Ozone) and Non-Selective Oxidants (Hydroxyl Radical). Water Research, 44, 555-566. https://doi.org/10.1016/j.watres.2009.11.045
von Gunten, U. (2007) The Basics of Oxidants in Water Treatment. Part B: Ozone reactions. Water Science & Technology, 55, 25-29. https://doi.org/10.2166/wst.2007.382
Hillaert, S. and Van den Bossche, W. (1999) Determination of Captopril and Its Degradation Products by Capillary Electrophoresis. Journal of Pharmaceutical and Biomedical Analysis, 21, 65-73. https://doi.org/10.1016/S0731-7085(99)00092-8
Mahmoud, W.M. and Kummerer, K. (2012) Captopril and Its Dimer Captopril Disulfide: Photodegradation, Aerobic Biodegradation and Identification of Transformation Products by HPLC-UV and LC-Ion Trap-MS(n). Chemosphere, 88, 1170-1177. https://doi.org/10.1016/j.chemosphere.2012.03.064
Small, Jr., W., Molteni, A., Kim, Y.T., Taylor, J.M., Ts'ao, C.H. and Ward, W.F. (1999) Mechanism of Captopril Toxicity to a Human Mammary Ductal Carcinoma Cell Line in the Presence of Copper. Breast Cancer Research and Treatment, 55, 223-229. https://doi.org/10.1023/A:1006233521325
Mascolo, G., Lopez, A., Detomaso, A. and Lovecchio, G. (2005) Ion Chromatography-Electrospray Mass Spectrometry for the Identification of Low-Molecular-Weight Organic Acids during the 2,4-Dichlorophenol Degradation. Journal of Chromatography A, 1067, 191-196. https://doi.org/10.1016/j.chroma.2004.12.058
Hart, E.J., Sehested, K. and Holoman, J. (1983) Molar Absorptivities of Ultraviolet and Visible Bands of Ozone in Aqueous Solutions. Analytical Chemistry, 55, 46-49. https://doi.org/10.1021/ac00252a015
Trovó, A.G., Pupo Nogueira, R.F., Agüera, A., Fernandez-Alba, A.R. and Malato, S. (2011) Degradation of the Antibiotic Amoxicillin by Photo-Fenton Process—Chemical and Toxicological Assessment. Water Research, 45, 1394-1402. https://doi.org/10.1016/j.watres.2010.10.029
da Silva, J.C., Teodoro, J.A., Afonso, R.J., Aquino, S.F. and Augusti, R. (2014) Photolysis and Photocatalysis of Ibuprofen in Aqueous Medium: Characterization of By-Products via Liquid Chromatography Coupled to High-Resolution Mass Spectrometry and Assessment of Their Toxicities against Artemia salina. Journal of Mass Spectrometry, 49, 145-153. https://doi.org/10.1002/jms.3320
da Silva, J.C., Reis Teodoro, J.A., Afonso, R.J., Aquino, S.F. and Augusti. R. (2014) Photodegradation of Bisphenol A in Aqueous Medium: Monitoring and Identification of By-Products by Liquid Chromatography Coupled to High-Resolution Mass Spectrometry. Rapid Communications in Mass Spectrometry, 28, 987-994. https://doi.org/10.1002/rcm.6863
e Freitas, J.R.L., Quintao, F.J.O., Silva, J.C.C.D., Silva, S.D.Q., Aquino, S.F. and Afonso, R.J.D.C.F. (2017) Characterisation of Captopril Photolysis and Photocatalysis By-Products in Water by Direct Infusion, Electrospray Ionisation, High-Resolution Mass Spectrometry and the Assessment of Their Toxicities. International Journal of Environmental Analytical Chemistry, 96, 1074-1090.
Quintao, F.J., Freitas, J.R., de Fatima Machado, C., Aquino, S.F., de Queiroz Silva, S. and de Cassia Franco Afonso, R.J. (2016) Characterization of Metformin By-Products under Photolysis, Photocatalysis, Ozonation and Chlorination by High Performance Liquid Chromatography Coupled to High-Resolution Mass Spectrometry (HPLC/HRMS). Rapid Communications in Mass Spectrometry. https://doi.org/10.1002/rcm.7724
Mosmann, T. (1983) Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. Journal of Immunological Methods, 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
Freimoser, F.M., Jakob, C.A., Aebi, M. and Tuor, U. (1999) The MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] Assay Is a Fast and Reliable Method for Colorimetric Determination of Fungal Cell Densities. Applied and Environmental Microbiology, 65, 3727-3729.
Zegura, B., Heath, E., Cernosa, A. and Filipic, M. (2009) Combination of In Vitro Bioassays for the Determination of Cytotoxic and Genotoxic Potential of Wastewater, Surface Water and Drinking Water Samples. Chemosphere, 75, 1453-1460. https://doi.org/10.1016/j.chemosphere.2009.02.041
Gerlier, D. and Thomasset, N. (1986) Use of MTT Colorimetric Assay to Measure Cell Activation. Journal of Immunological Methods, 94, 57-63. https://doi.org/10.1016/0022-1759(86)90215-2
Deborde, M. and von Gunten, U. (2008) Reactions of Chlorine with Inorganic and Organic Compounds during Water Treatment—Kinetics and Mechanisms: A critical Review. Water Research, 42, 13-51. https://doi.org/10.1016/j.watres.2007.07.025
Schymanski, E.L., Jeon, J., Gulde, R., Fenner, K., Ruff, M., Singer, H.P. and Hollender, J. (2014) Identifying Small Molecules via High Resolution Mass Spectrometry: Communicating Confidence. Environmental Science & Technology, 48, 2097-2098. https://doi.org/10.1021/es5002105