Development, Validation and Application of a Targeted LC-MS Method for Quantification of Microcystins and Nodularin: Towards a Better Characterization of Drinking Water
Van Hassel, Wannes; Huybrechts, Bart; Masquelier, Julienet al.
Water Science and Technology; Aquatic Science; Geography, Planning and Development; Biochemistry
Abstract :
[en] Cyanotoxins can be produced in surface waters by cyanobacterial blooms, mostly during summer and early autumn. Intoxications would result from consumption of water contaminated with the potent hepatotoxins, microcystins and nodularin. Therefore, the WHO has set a guideline value for drinking water quality concerning one congener of microcystin. Consequently, the design of a validated, public reference method to detect and quantify the hepatotoxins in drinking water is necessary. During this study, a method was developed to quantify cyanotoxins (eight microcystin congeners and nodularin) in water using liquid chromatography coupled with tandem mass spectrometry. Additionally, bottled and tap water samples were tested for the presence of cyanotoxins. No cyanotoxins were detected in any of the collected water samples. However, quality controls and the results of a proficiency test show the validity of the method.
Research Center/Unit :
InBios - Integrative Biological Sciences - ULiège Toxins - Service Organic contaminants and additives - Sciensano Risk and -Health Impact Assessment, Sciensano
Development, Validation and Application of a Targeted LC-MS Method for Quantification of Microcystins and Nodularin: Towards a Better Characterization of Drinking Water
AFSCA - Agence Fédérale pour la Sécurité de la Chaîne Alimentaire [BE] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Commentary :
In the current version of the text, a mistake was made in the associations of the authors. Our co-author Bart sadly passed away during the writing of the publication. Therefore, a cross has been placed next to his name. During the editing process, a cross was also placed next to the name of the first author. However, the first author is still alive and in good health. We expect this mistake will be fixed in the future.
Boergens, E.; Güntner, A.; Dobslaw, H.; Dahle, C. Quantifying the Central European Droughts in 2018 and 2019 with GRACE Follow-On. Geophys. Res. Lett. 2020, 47, e2020GL087285. [CrossRef]
Peeters, B. Waterverbruik Landbouw. 2021. Available online: https://www.vmm.be/sectoren/landbouw/waterverbruik-landbouw (accessed on 24 February 2022).
Vlaamse Milieumaatschappij Drinkwaterbalans Voor Vlaanderen. 2018. Available online: https://www.vmm.be/publicaties/drinkwaterbalans-voor-vlaanderen-2018#:~{}:text=In%202018%20werd%20367%2C0,2018%205%25%20minder% 20drinkwater%20geproduceerd (accessed on 24 February 2022).
Vlaamse Milieumaatschappij Drinkwaterbalans Voor Vlaanderen. 2019. Available online: https://publicaties.vlaanderen.be/view-file/40084#:~{}:text=In%202019%20werd%20in%20totaal,m%C2%B3%20is%20grondwater%20uit%20Walloni%C3%AB (accessed on 16 November 2021).
Direction des Eaux Souterraines. Direction de la Coordination des Données Qualite des Eaux Distribuees par le Reseau Public en Wallonie. 2018. Available online: http://environnement.wallonie.be/de/eso/eau_distribution/pdf/eau_distribution.pdf (accessed on 15 December 2020).
Brahy, V.; Huart, M.; T’serstevens, J.-J. L’Exploitation des Ressources en Eau de Surface; Institut Numérique. 2013. Available online: https://www.institut-numerique.org/49-exploitation-des-ressources-en-eau-de-surface-52315bfe26de0 (accessed on 18 November 2021).
État de l’Environnement Wallon. Production d’Eau de Distribution. Available online: http://etat.environnement.wallonie.be/contents/indicatorsheets/RESS%203.html (accessed on 18 November 2021).
Peeters, B. Drinkwaterwinning. 2019. Available online: https://www.milieurapport.be/downloads/9156c60dfb7444158616fc887 976dd97/1575968500/drinkwaterwinning.pdf (accessed on 15 December 2020).
Descy, J.-P.; Leprieur, F.; Pirlot, S.; Leporcq, B.; Van Wichelen, J.; Peretyatko, A.; Teissier, S.; Codd, G.A.; Triest, L.; Vyverman, W.; et al. Identifying the Factors Determining Blooms of Cyanobacteria in a Set of Shallow Lakes. Ecol. Inform. 2016, 34, 129–138. [CrossRef]
O’Neil, J.M.; Davis, T.W.; Burford, M.A.; Gobler, C.J. The Rise of Harmful Cyanobacteria Blooms: The Potential Roles of Eutrophication and Climate Change. Harmful Algae 2012, 14, 313–334. [CrossRef]
Mantzouki, E.; Lürling, M.; Fastner, J.; de Senerpont Domis, L.; Wilk-Wo’zniak, E. Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins. Toxins 2018, 10, 156. [CrossRef]
Mazur-Marzec, H.; Sutryk, K.; Kobos, J.; Hebel, A.; Hohlfeld, N.; Błaszczyk, A.; Toruńska, A.; Kaczkowska, M.J.; Łysiak-Pastuszak, E.; Kraśniewski, W.; et al. Occurrence of Cyanobacteria and Cyanotoxin in the Southern Baltic Proper. Filamentous Cyanobacteria versus Single-Celled Picocyanobacteria. Hydrobiologia 2013, 701, 235–252. [CrossRef]
MacKintosh, C.; Beattie, K.A.; Klumpp, S.; Cohen, P.; Codd, G.A. Cyanobacterial Microcystin-LR is a Potent and Specific Inhibitor of Protein Phosphatases 1 and 2A from Both Mammals and Higher Plants. FEBS Lett. 1990, 264, 187–192. [CrossRef]
Runnegar, M.T.; Kong, S.; Berndt, N. Protein Phosphatase Inhibition and in Vivo Hepatotoxicity of Microcystins. Am. J. Physiol.-Gastrointest. Liver Physiol. 1993, 265, G224–G230. [CrossRef]
Fischer, A.; Hoeger, S.J.; Stemmer, K.; Feurstein, D.J.; Knobeloch, D.; Nussler, A.; Dietrich, D.R. The Role of Organic Anion Transporting Polypeptides (OATPs/SLCOs) in the Toxicity of Different Microcystin Congeners in Vitro: A Comparison of Primary Human Hepatocytes and OATP-Transfected HEK293 Cells. Toxicol. Appl. Pharmacol. 2010, 245, 9–20. [CrossRef]
Dahlmann, J.; Rühl, A.; Hummert, C.; Liebezeit, G.; Carlsson, P.; Granéli, E. Different Methods for Toxin Analysis in the Cyanobacterium Nodularia Spumigena (Cyanophyceae). Toxicon 2001, 39, 1183–1190. [CrossRef]
An, J.; Carmichael, W.W. Use of a Colorimetric Protein Phosphatase Inhibition Assay and Enzyme Linked Immunosorbent Assay for the Study of Microcystins and Nodularins. Toxicon 1994, 32, 1495–1507. [CrossRef]
Svirčev, Z.; Lalić, D.; Bojadzija Savic, G.; Tokodi, N.; Drobac Backovic, D.; Chen, L.; Meriluoto, J.; Codd, G. Global Geographical and Historical Overview of Cyanotoxin Distribution and Cyanobacterial Poisonings. Arch. Toxicol. 2019, 93, 2429–2481. [CrossRef]
World Health Organization. Cyanobacterial Toxins: Microcystins. Background Document for Development of WHO Guidelines for Drinking-Water Quality and Guidelines for Safe Recreational Water Environments; World Health Organization: Geneva, Switzerland, 2020.
Fawell, J.K.; Mitchell, R.E.; Everett, D.J.; Hill, R.E. The Toxicity of Cyanobacterial Toxins in the Mouse: I Microcystin-LR. Hum. Exp. Toxicol. 1999, 18, 162–167. [CrossRef] [PubMed]
Directive (EU) 2020/2184 of the European Parliament and of the Council of 16 December 2020 on the Quality of Water Intended for Human Consumption; EUR-Lex: Brussels, Belgium, 2020.
Lawton, L.A.; Edwards, C.; Codd, G.A. Extraction and High-Performance Liquid Chromatographic Method for the Determination of Microcystins in Raw and Treated Waters. Analyst 1994, 119, 1525. [CrossRef]
Chu, F.S.; Huang, X.; Wei, R.D.; Carmichael, W.W. Production and Characterization of Antibodies against Microcystins. Appl. Environ. Microbiol. 1989, 55, 1928–1933. [CrossRef] [PubMed]
Kleinteich, J.; Id, J.P.; Id, S.A.W.; Id, F.H.; Laughinghouse, H.D.; Id, I.V.; Pearce, D.A.; Dietrich, D.R.; Wilmotte, A. Toxic Cyanobacteria in Svalbard: Chemical Diversity of Microcystins Detected Using a Precursor Ion Screening Method. Toxins 2018, 10, 147. [CrossRef]
Spoof, L.; Vesterkvist, P.; Lindholm, T.; Meriluoto, J. Screening for Cyanobacterial Hepatotoxins, Microcystins and Nodularin in Environmental Water Samples by Reversed-Phase Liquid Chromatography-Electrospray Ionisation Mass Spectrometry. J. Chromatogr. A 2003, 1020, 105–119. [CrossRef]
Turner, A.D.; Waack, J.; Lewis, A.; Edwards, C.; Lawton, L. Development and Single-Laboratory Validation of a UHPLC-MS/MS Method for Quantitation of Microcystins and Nodularin in Natural Water, Cyanobacteria, Shellfish and Algal Supplement Tablet Powders. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2018, 1074–1075, 111–123. [CrossRef]
Zervou, S.-K.; Christophoridis, C.; Kaloudis, T.; Triantis, T.M.; Hiskia, A. New SPE-LC-MS/MS Method for Simultaneous Determination of Multi-Class Cyanobacterial and Algal Toxins. J. Hazard. Mater. 2017, 323, 56–66. [CrossRef]
Pekar, H.; Westerberg, E.; Bruno, O.; Lääne, A.; Persson, K.M.; Sundström, L.F.; Thim, A.M. Fast, Rugged and Sensitive Ultra High Pressure Liquid Chromatography Tandem Mass Spectrometry Method for Analysis of Cyanotoxins in Raw Water and Drinking Water—First Findings of Anatoxins, Cylindrospermopsins and Microcystin Variants in Swedish Source Wa. J. Chromatogr. A 2016, 1429, 265–276. [CrossRef] [PubMed]
Funk, W.; Dammann, V.; Donnevert, G. Quality Assurance in Analytical Chemistry, 2nd ed.; WILEY: Weinheim, Germany, 2007.
2002/657/EC: Commission Decision of 12 August 2002 Implementing Council Directive 96/23/EC Concerning the Performance of Analytical Methods and the Interpretation of Results (Text with EEA Relevance) (Notified under Document Number C(2002) 3044). Available online: http://op.europa.eu/en/publication-detail/-/publication/ed928116-a955-4a84-b10a-cf7a82bad858/language-en (accessed on 30 November 2020).
Van Loco, J.; Elskens, M.; Croux, C.; Beernaert, H. Linearity of Calibration Curves: Use and Misuse of the Correlation Coefficient. Accredit. Qual. Assur. 2002, 7, 281–285. [CrossRef]
Altaner, S.; Puddick, J.; Fessard, V.; Feurstein, D.; Zemskov, I.; Wittmann, V.; Dietrich, D.R. Simultaneous Detection of 14 Mi-crocystin Congeners from Tissue Samples Using UPLC-ESI-MS/MS and Two Different Deuterated Synthetic Microcystins as Internal Standards. Toxins 2019, 11, 388. [CrossRef] [PubMed]
Díez-Quijada, L.; Guzmán-Guillén, R.; Prieto Ortega, A.I.; Llana-Ruíz-Cabello, M.; Campos, A.; Vasconcelos, V.; Jos, Á.; Cameán, A.M. New Method for Simultaneous Determination of Microcystins and Cylindrospermopsin in Vegetable Matrices by SPE-UPLC-MS/MS. Toxins 2018, 10, 406. [CrossRef]
Altaner, S.; Puddick, J.; Wood, S.A.; Dietrich, D.R. Adsorption of Ten Microcystin Congeners to Common Laboratory-Ware is Solvent and Surface Dependent. Toxins 2017, 9, 129. [CrossRef]
Vlaamse Milieu Maatschappij (VMM). Status Indicator Bevoorrading Leidingwater: Situatie op 24/09/2020. Available online: https://www.dewatergroep.be/nl-be/drinkwater/weetjes-en-tips/van-bron-tot-kraan/oppervlaktewater#:~{}: text=Van%20oppervlaktewater%20tot%20drinkwater&text=Die%20behandeling%20gebeurt%20in%20het,gebied%20en%20 dus%20drinkbaar%20wordt (accessed on 24 February 2022).
Dewatergroep Oppervlakte Water: Van Oppervlakte Water Naar Drink Water. Available online: https://www.dewatergroep.be/nl-be/drinkwater/weetjes-en-tips/van-bron-tot-kraan/oppervlaktewater (accessed on 24 February 2022).
Pitois, F.; Fastner, J.; Pagotto, C.; Dechesne, M. Multi-Toxin Occurrences in Ten French Water Resource Reservoirs. Toxins 2018, 10, 283. [CrossRef]
USEPA. Recommendations for Public Water Systems to Manage Cyanotoxins in Drinking Water; USEPA: Washington, DC, USA, 2015.
Hummert, C.; Reichelt, M.; Weiß, J.; Liebert, H.P.; Luckas, B. Identification of Microcystins in Cyanobacteria from the Bleiloch Former Drinking-Water Reservoir (Thuringia, Germany). Chemosphere 2001, 44, 1581–1588. [CrossRef]
Teneva, I.; Mladenov, R.; Belkinova, D.; Dimitrova-Dyulgerova, I.; Dzhambazov, B. Phytoplankton Community of the Drinking Water Supply Reservoir Borovitsa (South Bulgaria) with an Emphasis on Cyanotoxins and Water Quality. Open Life Sci. 2010, 5, 231–239. [CrossRef]
Beversdorf, L.J.; Rude, K.; Weirich, C.A.; Bartlett, S.L.; Seaman, M.; Kozik, C.; Biese, P.; Gosz, T.; Suha, M.; Stempa, C.; et al. Analysis of Cyanobacterial Metabolites in Surface and Raw Drinking Waters Reveals More than Microcystin. Water Res. 2018, 140, 280–290. [CrossRef]
Czyżewska, W.; Piontek, M.; Łuszczyńska, K. The Occurrence of Potential Harmful Cyanobacteria and Cyanotoxins in the Obrzyca River (Poland), a Source of Drinking Water. Toxins 2020, 12, 284. [CrossRef] [PubMed]
Ballot, A.; Swe, T.; Mjelde, M.; Cerasino, L.; Hostyeva, V.; Miles, C.O. Cylindrospermopsin-and Deoxycylindrospermopsin-Producing Raphidiopsis Raciborskii and Microcystin-Producing Microcystis spp. in Meiktila Lake, Myanmar. Toxins 2020, 12, 232. [CrossRef] [PubMed]
Tamele, I.J.; Vasconcelos, V. Microcystin Incidence in the Drinking Water of Mozambique: Challenges for Public Health Protection. Toxins 2020, 12, 368. [CrossRef] [PubMed]
Ribau Teixeira, M.; Rosa, M.J. Neurotoxic and Hepatotoxic Cyanotoxins Removal by Nanofiltration. Water Res. 2006, 40, 2837–2846. [CrossRef] [PubMed]
Hoeger, S.J.; Shaw, G.; Hitzfeld, B.C.; Dietrich, D.R. Occurrence and Elimination of Cyanobacterial Toxins in Two Australian Drinking Water Treatment Plants. Toxicon 2004, 43, 639–649. [CrossRef]
Pendleton, P.; Schumann, R.; Wong, S.H. Microcystin-LR Adsorption by Activated Carbon. J. Colloid Interface Sci. 2001, 240, 1–8. [CrossRef]
Ho, L.; Lambling, P.; Bustamante, H.; Duker, P.; Newcombe, G. Application of Powdered Activated Carbon for the Adsorption of Cylindrospermopsin and Microcystin Toxins from Drinking Water Supplies. Water Res. 2011, 45, 2954–2964. [CrossRef]
Huang, W.-J.; Cheng, B.-L.; Cheng, Y.-L. Adsorption of Microcystin-LR by Three Types of Activated Carbon. J. Hazard. Mater. 2007, 141, 115–122. [CrossRef]
Cook, D.; Newcombe, G. Removal of Microcystin Variants with Powdered Activated Carbon. Water Supply 2002, 2, 201–207. [CrossRef]
Cook, D.; Newcombe, G.; Sztajnbok, P. The Application of Powdered Activated Carbon for Mib and Geosmin Removal: Predicting Pac Doses in Four Raw Waters. Water Res. 2001, 35, 1325–1333. [CrossRef]
Clasen, J.; Mischke, U.; Drikas, M.; Chow, C. An Improved Method for Detecting Electrophoretic Mobility of Algae during the Destabilisation Process of Flocculation: Flocculant Demand of Different Species and the Impact of DOC. J. Water Supply Res. Technol.-AQUA 2000, 49, 89–101. [CrossRef]
Abbas, T.; Kajjumba, G.W.; Ejjada, M.; Masrura, S.U.; Marti, E.J.; Khan, E.; Jones-Lepp, T.L. Recent Advancements in the Removal of Cyanotoxins from Water Using Conventional and Modified Adsorbents—A Contemporary Review. Water 2020, 12, 2756. [CrossRef]
Westrick, J.A.; Szlag, D.C.; Southwell, B.J.; Sinclair, J. A Review of Cyanobacteria and Cyanotoxins Removal/Inactivation in Drinking Water Treatment. Anal. Bioanal. Chem. 2010, 397, 1705–1714. [CrossRef] [PubMed]
Acero, J.L.; Rodriguez, E.; Meriluoto, J. Kinetics of Reactions between Chlorine and the Cyanobacterial Toxins Microcystins. Water Res. 2005, 39, 1628–1638. [CrossRef]
Daly, R.I.; Ho, L.; Brookes, J.D. Effect of Chlorination on Microcystis Aeruginosa Cell Integrity and Subsequent Microcystin Release and Degradation. Environ. Sci. Technol. 2007, 41, 4447–4453. [CrossRef]
Song, W.; de la Cruz, A.A.; Rein, K.; O’Shea, K.E. Ultrasonically Induced Degradation of Microcystin-LR and-RR: Identification of Products, Effect of PH, Formation and Destruction of Peroxides. Environ. Sci. Technol. 2006, 40, 3941–3946. [CrossRef]
Wert, E.C.; Dong, M.M.; Rosario-Ortiz, F.L. Using Digital Flow Cytometry to Assess the Degradation of Three Cyanobacteria Species after Oxidation Processes. Water Res. 2013, 47, 3752–3761. [CrossRef]
Newcombe, G.; Nicholson, B.C. Water Treatment Options for Dissolved Cyanotoxins. J. Water Supply Res. Technol.-AQUA 2004, 53, 227–239. [CrossRef]
Newcombe, G.; Nicholson, B. Treatment Options for the Saxitoxin Class of Cyanotoxins. Water Supply 2002, 2, 271–275. [CrossRef]
Sorlini, S.; Collivignarelli, C.; Carnevale Miino, M.; Caccamo, F.M.; Collivignarelli, M.C. Kinetics of Microcystin-LR Removal in a Real Lake Water by UV/H2O2 Treatment and Analysis of Specific Energy Consumption. Toxins 2020, 12, 810. [CrossRef] [PubMed]
Coral, L.A.; Zamyadi, A.; Barbeau, B.; Bassetti, F.J.; Lapolli, F.R.; Prévost, M. Oxidation of Microcystis Aeruginosa and Anabaena Flos-Aquae by Ozone: Impacts on Cell Integrity and Chlorination by-Product Formation. Water Res. 2013, 47, 2983–2994. [CrossRef] [PubMed]