{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T01:54:15Z","timestamp":1774403655614,"version":"3.50.1"},"reference-count":97,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\/MCTES","award":["UIDB\/50006\/202"],"award-info":[{"award-number":["UIDB\/50006\/202"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>In recent years, contaminants of emerging concern have been reported in several environmental matrices due to advances in analytical methodologies. These anthropogenic micropollutants are detected at residual levels, representing an ecotoxicological threat to aquatic ecosystems. In particular, the pharmacotherapeutic group of non-steroidal anti-inflammatories (NSAIDs) is one of the most prescribed and used, as well as one of the most frequently detected in the aquatic environment. Bivalves have several benefits as a foodstuff, and also as an environment bioindicator species. Therefore, they are regarded as an ideal tool to assess this issue from both ecotoxicological and food safety perspectives. Thus, the control of these residues in bivalves is extremely important to safeguard environmental health, also ensuring food safety and public health. This paper aims to review NSAIDs in bivalves, observing their consumption, physicochemical characteristics, and mechanisms of action; their environmental occurrence in the aquatic environment and aquatic biota; and their effects on the ecosystem and the existent legal framework. A review of the analytical methodologies for the determination of NSAIDs in bivalves is also presented.<\/jats:p>","DOI":"10.3390\/toxics12060415","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T10:05:50Z","timestamp":1717581950000},"page":"415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Non-Steroidal Anti-Inflammatory Drugs in the Aquatic Environment and Bivalves: The State of the Art"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7744-3198","authenticated-orcid":false,"given":"Pedro","family":"Pires","sequence":"first","affiliation":[{"name":"LAQV, REQUIMTE, Laboratory of Bromatology and Pharmacognosy, Faculty of Pharmacy, University of Coimbra, Polo III, Azinhaga de Sta Comba, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-4340","authenticated-orcid":false,"given":"Andr\u00e9 M. P. T.","family":"Pereira","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Laboratory of Bromatology and Pharmacognosy, Faculty of Pharmacy, University of Coimbra, Polo III, Azinhaga de Sta Comba, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-647X","authenticated-orcid":false,"given":"Angelina","family":"Pena","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Laboratory of Bromatology and Pharmacognosy, Faculty of Pharmacy, University of Coimbra, Polo III, Azinhaga de Sta Comba, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2372-1874","authenticated-orcid":false,"given":"Liliana J. G.","family":"Silva","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Laboratory of Bromatology and Pharmacognosy, Faculty of Pharmacy, University of Coimbra, Polo III, Azinhaga de Sta Comba, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.marenvres.2018.05.001","article-title":"Pharmaceuticals in the Aquatic Environments: Evidence of Emerged Threat and Future Challenges for Marine Organisms","volume":"140","author":"Mezzelani","year":"2018","journal-title":"Mar. Environ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3510","DOI":"10.1021\/acs.chemrev.8b00299","article-title":"Pharmaceuticals of Emerging Concern in Aquatic Systems: Chemistry, Occurrence, Effects, and Removal Methods","volume":"119","author":"Patel","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_3","first-page":"1115","article-title":"Microwave-Assisted Micellar Extraction Coupled with Solid- Phase Extraction for Preconcentration of Pharmaceuticals in Molluscs Prior to Determination by HPLC","volume":"1122","year":"2008","journal-title":"Biomed. Chromatogr."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pereira, A., Silva, L., Laranjeiro, C., Lino, C., and Pena, A. (2020). Selected Pharmaceuticals in Different Aquatic Compartments: Part I\u2014Source, Fate and Occurrence. Molecules, 25.","DOI":"10.3390\/molecules25051026"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1016\/j.chemosphere.2015.10.100","article-title":"Assessing Environmental Risk of Pharmaceuticals in Portugal: An Approach for the Selection of the Portuguese Monitoring Stations in Line with Directive 2013\/39\/EU","volume":"144","author":"Pereira","year":"2016","journal-title":"Chemosphere"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jhazmat.2009.10.100","article-title":"Ecotoxicological Aspects Related to the Presence of Pharmaceuticals in the Aquatic Environment","volume":"175","author":"Santos","year":"2010","journal-title":"J. Hazard. Mater."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1007\/s00296-011-2263-6","article-title":"A Turbulent Decade for NSAIDs: Update on Current Concepts of Classification, Epidemiology, Comparative Efficacy, and Toxicity","volume":"32","author":"Conaghan","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.envres.2015.02.016","article-title":"Seasonal Distribution of Pharmaceuticals in Marine Water and Sediment from a Mediterranean Coastal Lagoon (SE Spain)","volume":"138","author":"Gros","year":"2015","journal-title":"Environ. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.scitotenv.2017.06.076","article-title":"SSRIs Antidepressants in Marine Mussels from Atlantic Coastal Areas and Human Risk Assessment","volume":"603\u2013604","author":"Silva","year":"2017","journal-title":"Sci. Total Environ."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1038\/srep02646","article-title":"Size Matters: Implications of the Loss of Large Individuals for Ecosystem Function","volume":"3","author":"Norkko","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.foodcont.2014.01.017","article-title":"Portuguese Consumers\u2019 Attitudes and Perceptions of Bivalve Molluscs","volume":"41","author":"Anacleto","year":"2014","journal-title":"Food Control"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gosling, E.M. (2003). Bivalve Molluscs: Biology, Ecology, and Culture, Wiley-Blackwell. Fishing News Books.","DOI":"10.1002\/9780470995532"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.envpol.2018.02.018","article-title":"Effects of Water Warming and Acidification on Bioconcentration, Metabolization and Depuration of Pharmaceuticals and Endocrine Disrupting Compounds in Marine Mussels (Mytilus Galloprovincialis)","volume":"236","author":"Maulvault","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.talanta.2014.12.035","article-title":"Multi-Residue Method for the Analysis of Pharmaceuticals and Some of Their Metabolites in Bivalves","volume":"136","author":"Huerta","year":"2015","journal-title":"Talanta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1128\/CMR.00059-09","article-title":"Epidemiology of Seafood-Associated Infections in the United States","volume":"23","author":"Iwamoto","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1365-277X.2004.00552.x","article-title":"The Health Benefits of Omega-3 Polyunsaturated Fatty Acids: A Review of the Evidence","volume":"17","author":"Ruxton","year":"2004","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yaghubi, E., Carboni, S., Snipe, R.M.J., Shaw, C.S., Fyfe, J.J., Smith, C.M., Kaur, G., Tan, S.Y., and Hamilton, D.L. (2021). Farmed Mussels: A Nutritive Protein Source, Rich in Omega-3 Fatty Acids, with a Low Environmental Footprint. Nutrients, 13.","DOI":"10.3390\/nu13041124"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"125907","DOI":"10.1016\/j.foodchem.2019.125907","article-title":"Bivalves as Future Source of Sustainable Natural Omega-3 Polyunsaturated Fatty Acids","volume":"311","author":"Tan","year":"2020","journal-title":"Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.fm.2017.12.006","article-title":"Escherichia Coli Testing and Enumeration in Live Bivalve Shellfish\u2014Present Methods and Future Directions","volume":"73","author":"Walker","year":"2018","journal-title":"Food Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5812","DOI":"10.1128\/AEM.01046-12","article-title":"Two-Year Systematic Study to Assess Norovirus Contamination in Oysters from Commercial Harvesting Areas in the United Kingdom","volume":"78","author":"Lowther","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.envpol.2016.04.012","article-title":"Microplastics in Mussels along the Coastal Waters of China","volume":"214","author":"Li","year":"2016","journal-title":"Environ. Pollut."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1002\/etc.5046","article-title":"A Simple and Rapid UHPLC-MS\/MS Method for the Quantitation of Pharmaceuticals and Related Compounds in Mussels and Oysters","volume":"40","author":"Maskrey","year":"2021","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9509","DOI":"10.1007\/s00216-013-7371-6","article-title":"The Determination of Pharmaceutical Residues in Cooked and Uncooked Marine Bivalves Using Pressurised Liquid Extraction, Solid-Phase Extraction and Liquid Chromatography\u2013Tandem Mass Spectrometry","volume":"405","author":"McEneff","year":"2013","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1080\/21553769.2016.1162753","article-title":"Bioindicators: The Natural Indicator of Environmental Pollution","volume":"9","author":"Parmar","year":"2016","journal-title":"Front. Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"114442","DOI":"10.1016\/j.envpol.2020.114442","article-title":"Anti-Inflammatory Drugs in the Marine Environment: Bioconcentration, Metabolism and Sub-Lethal Effects in Marine Bivalves","volume":"263","author":"Almeida","year":"2020","journal-title":"Environ. Pollut."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.envres.2015.09.018","article-title":"Occurrence of Pharmaceuticals and Endocrine Disrupting Compounds in Macroalgaes, Bivalves, and Fish from Coastal Areas in Europe","volume":"143","author":"Maulvault","year":"2015","journal-title":"Environ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.jenvman.2013.12.017","article-title":"Bioaccumulation and Biomagnification Potential of Pharmaceuticals with a Focus to the Aquatic Environment","volume":"133","author":"Zenker","year":"2014","journal-title":"J. Environ. Manag."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0049-3848(03)00379-7","article-title":"The Mechanism of Action of Aspirin","volume":"110","author":"Vane","year":"2003","journal-title":"Thromb. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.18433\/J3T886","article-title":"Evolution of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Cyclooxygenase (COX) Inhibition and Beyond","volume":"11","author":"Knaus","year":"2008","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.envint.2008.10.008","article-title":"Occurrence and Fate of Pharmaceutical Products and By-Products, from Resource to Drinking Water","volume":"35","author":"Mompelat","year":"2009","journal-title":"Environ. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/newbio231232a0","article-title":"Inhibition of Prostaglandin Synthesis as a Mechanism of Action for Aspirin-like Drugs","volume":"231","author":"Vane","year":"1971","journal-title":"Nat. New Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1152\/physrev.1999.79.4.1193","article-title":"Prostanoid Receptors: Structures, Properties, and Functions","volume":"79","author":"Narumiya","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/1-4020-5688-5_1","article-title":"Anti-Inflammatory Drugs in the 21st Century","volume":"42","author":"Rainsford","year":"2007","journal-title":"Subcell. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ishiguro, H., and Kawahara, T. (2014). Nonsteroidal Anti-Inflammatory Drugs and Prostatic Diseases. Biomed Res. Int., 2014.","DOI":"10.1155\/2014\/436123"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"143","DOI":"10.14336\/AD.2017.0306","article-title":"A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly","volume":"9","author":"Wongrakpanich","year":"2018","journal-title":"Aging Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nunes, B., Daniel, D., Canelas, G.G., Barros, J., and Correia, A.T. (2020). Toxic Effects of Environmentally Realistic Concentrations of Diclofenac in Organisms from Two Distinct Trophic Levels, Hediste Diversicolor and Solea Senegalensis. Comp. Biochem. Physiol. Part C Toxicol. Pharmacol., 231.","DOI":"10.1016\/j.cbpc.2020.108722"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.scitotenv.2016.08.089","article-title":"Presence of Pharmaceuticals in the Lis River (Portugal): Sources, Fate and Seasonal Variation","volume":"573","author":"Santos","year":"2016","journal-title":"Sci. Total Environ."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.seppur.2010.11.020","article-title":"Removal of Pharmaceuticals and Endocrine Disrupting Compounds in a Water Recycling Process Using Reverse Osmosis Systems","volume":"77","author":"Khabbaz","year":"2011","journal-title":"Sep. Purif. Technol."},{"key":"ref_39","unstructured":"(2024, April 18). Knappe Project. 2008. Knappe Project. (2008). KNAPPE: Knowledge and Need Assessment on Pharmaceutical Products in Environmental Waters\u2014Final Report. Available online: https:\/\/cordis.europa.eu\/docs\/results\/36\/36864\/124584761-6_en.pdf."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ecoenv.2016.10.029","article-title":"Ecological Risk Assessment of Pharmaceuticals in the Receiving Environment of Pharmaceutical Wastewater in Pakistan","volume":"136","author":"Ashfaq","year":"2017","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.scitotenv.2018.07.240","article-title":"Environmental Loadings of Active Pharmaceutical Ingredients from Manufacturing Facilities in Canada","volume":"646","author":"Kleywegt","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jchromb.2013.04.032","article-title":"Development of a Simple Analytical Method for the Simultaneous Determination of Paracetamol, Paracetamol-Glucuronide and p-Aminophenol in River Water","volume":"930","author":"Santos","year":"2013","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14717","DOI":"10.1007\/s11356-017-9012-7","article-title":"Occurrence and Behaviour of Pharmaceutical Compounds in a Portuguese Wastewater Treatment Plant: Removal Efficiency through Conventional Treatment Processes","volume":"24","author":"Cardoso","year":"2017","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.ijheh.2019.05.006","article-title":"Occurrence of Selected Pharmaceuticals in Wastewater Treatment Plants of Tuscany: An Effect-Based Approach to Evaluate the Potential Environmental Impact","volume":"222","author":"Palli","year":"2019","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1016\/j.watres.2010.05.032","article-title":"Pan-European Survey on the Occurrence of Selected Polar Organic Persistent Pollutants in Ground Water","volume":"44","author":"Loos","year":"2010","journal-title":"Water Res."},{"key":"ref_46","first-page":"415","article-title":"Determination of 81 Pharmaceutical Drugs by High Performance Liquid Chromatography Coupled to Mass Spectrometry with Hybrid Triple Quadrupole-Linear Ion Trap in Different Types of Water in Serbia","volume":"468\u2013469","author":"Barcelo","year":"2014","journal-title":"Sci. Total Environ."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s10661-015-4497-3","article-title":"Occurrence of Pharmaceuticals, Hormones, and Perfluorinated Compounds in Groundwater in Taiwan","volume":"187","author":"Lin","year":"2015","journal-title":"Environ. Monit. Assess."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.scitotenv.2012.06.027","article-title":"Occurrence and Distribution of Multi-Class Pharmaceuticals and Their Active Metabolites and Transformation Products in the Ebro River Basin (NE Spain)","volume":"440","year":"2012","journal-title":"Sci. Total Environ."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.scitotenv.2014.11.097","article-title":"Assessment of Non-Steroidal Anti-Inflammatory and Analgesic Pharmaceuticals in Seawaters of North of Portugal: Occurrence and Environmental Risk","volume":"508","author":"Santos","year":"2015","journal-title":"Sci. Total Environ."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.talanta.2010.09.046","article-title":"Fully Automated Determination of 74 Pharmaceuticals in Environmental and Waste Waters by Online Solid Phase Extraction-Liquid Chromatography-Electrospray-Tandem Mass Spectrometry","volume":"83","author":"Ginebreda","year":"2010","journal-title":"Talanta"},{"key":"ref_51","unstructured":"(2024, April 18). TemaNord. PPCP Monitoring in the Nordic Countries-Status Report; 2012. Available online: http:\/\/norden.diva-portal.org\/smash\/record.jsf?pid=diva2%3A702823&dswid=-171."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4978","DOI":"10.1007\/s11356-014-3617-x","article-title":"Occurrence of PPCPs in the Marine Environment: A Review","volume":"23","author":"Gomez","year":"2016","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.envpol.2018.04.012","article-title":"A Review of the Pharmaceutical Exposome in Aquatic Fauna","volume":"239","author":"Miller","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.scitotenv.2013.12.123","article-title":"A Year-Long Study of the Spatial Occurrence and Relative Distribution of Pharmaceutical Residues in Sewage Effluent, Receiving Marine Waters and Marine Bivalves","volume":"476\u2013477","author":"McEneff","year":"2014","journal-title":"Sci. Total Environ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s00216-011-4878-6","article-title":"Development of Analytical Strategies Using U-HPLC-MS\/MS and LC-ToF-MS for the Quantification of Micropollutants in Marine Organisms","volume":"400","author":"Wille","year":"2011","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.marenvres.2016.03.005","article-title":"Ecotoxicological Potential of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in Marine Organisms: Bioavailability, Biomarkers and Natural Occurrence in Mytilus Galloprovincialis","volume":"121","author":"Mezzelani","year":"2016","journal-title":"Mar. Environ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"149744","DOI":"10.1016\/j.scitotenv.2021.149744","article-title":"Occurrence of Pharmaceuticals in Seafood from Two Brazilian Coastal Areas: Implication for Human Risk Assessment","volume":"803","author":"Mello","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1007\/s12161-018-01418-y","article-title":"Development of a Multiresidue Method for the Determination of 24 Pharmaceuticals in Clams by QuEChERS and Liquid Chromatography-Triple Quadrupole Tandem Mass Spectrometry","volume":"12","author":"Rodrigues","year":"2019","journal-title":"Food Anal. Methods"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.envpol.2017.02.061","article-title":"Mussels as Bioindicators of Diclofenac Contamination in Coastal Environments","volume":"225","author":"Cunha","year":"2017","journal-title":"Environ. Pollut."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.envpol.2016.12.026","article-title":"Bioaccumulation and Trophic Transfer of Pharmaceuticals in Food Webs from a Large Freshwater Lake","volume":"222","author":"Xie","year":"2017","journal-title":"Environ. Pollut."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.talanta.2019.03.062","article-title":"Simultaneous Determination of Non-Steroidal Anti-Inflammatory Drugs and Natural Estrogens in the Mussels Mytilus Edulis Trossulus","volume":"200","author":"Wolecki","year":"2019","journal-title":"Talanta"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.envint.2013.01.009","article-title":"Method Validation and Reconnaissance of Pharmaceuticals, Personal Care Products, and Alkylphenols in Surface Waters, Sediments, and Mussels in an Urban Estuary","volume":"54","author":"Klosterhaus","year":"2013","journal-title":"Environ. Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1007\/s00216-012-6144-y","article-title":"Pharmaceuticals in Biota in the Aquatic Environment: Analytical Methods and Environmental Implications","volume":"404","author":"Huerta","year":"2012","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_64","unstructured":"N\u00fa\u00f1ez Marc\u00e9, M. (2017). Emerging Organic Contaminants in Aquatic Organisms, Universitat Rovira i Virgili."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.talanta.2016.04.016","article-title":"Development of a Multi-Residue Analysis of Diclofenac and Some Transformation Products in Bivalves Using QuEChERS Extraction and Liquid Chromatography-Tandem Mass Spectrometry. Application to Samples from Mesocosm Studies","volume":"155","author":"Daniele","year":"2016","journal-title":"Talanta"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Pereira, A., Silva, L., Laranjeiro, C., Lino, C., and Pena, A. (2020). Selected Pharmaceuticals in Different Aquatic Compartments: Part II\u2014Toxicity and Environmental Risk Assessment. Molecules, 25.","DOI":"10.3390\/molecules25081796"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"136804","DOI":"10.1016\/j.scitotenv.2020.136804","article-title":"Combined Effects of Salinity Changes and Salicylic Acid Exposure in Mytilus Galloprovincialis","volume":"715","author":"Freitas","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.scitotenv.2018.06.125","article-title":"Diclofenac Affects Early Embryo Development in the Marine Bivalve Mytilus Galloprovincialis","volume":"642","author":"Balbi","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"104167","DOI":"10.1016\/j.etap.2023.104167","article-title":"Single and Combined Effects of Caffeine and Salicylic Acid on Mussel Mytilus Galloprovincialis: Changes at Histomorphological, Molecular and Biochemical Levels","volume":"101","author":"Afsa","year":"2023","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5553","DOI":"10.1007\/s00216-015-8760-9","article-title":"Direct Injection of Tissue Extracts in Liquid Chromatography\/Tandem Mass Spectrometry for the Determination of Pharmaceuticals and Other Contaminants of Emerging Concern in Mollusks","volume":"407","author":"Bayen","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"#cr-split#-ref_71.1","unstructured":"European Commission (2006). Commission Regulation"},{"key":"#cr-split#-ref_71.2","unstructured":"(EC) No 1881\/2006 of 19 December 2006 Setting Maximum Levels for Certain Contaminants in Foodstuffs. Off. J. Eur. Union, 49, 5-24."},{"key":"ref_72","unstructured":"European Commission (2022). COMMISSION REGULATION (EU) 2022\/1370 of 5 August 2022 Amending Regulation (EC) No 1881\/2006 as Regards Maximum Levels of Ochratoxin A in Certain Foodstuffs. Off. J. Eur. Union, L206, 11\u201314."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.envres.2015.06.011","article-title":"Environmental Contaminants of Emerging Concern in Seafood\u2014European Database on Contaminant Levels","volume":"143","author":"Vandermeersch","year":"2015","journal-title":"Environ. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.scitotenv.2018.08.309","article-title":"Monitoring of the 17 EU Watch List Contaminants of Emerging Concern in the Ave and the Sousa Rivers","volume":"649","author":"Sousa","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00216-018-1474-z","article-title":"Multiresidue Analytical Method for the Determination of 41 Multiclass Organic Pollutants in Mussel and Fish Tissues and Biofluids by Liquid Chromatography Coupled to Tandem Mass Spectrometry","volume":"411","author":"Mijangos","year":"2019","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.chroma.2013.06.071","article-title":"Fast and Easy Extraction Combined with High Resolution-Mass Spectrometry for Residue Analysis of Two Anticonvulsants and Their Transformation Products in Marine Mussels","volume":"1305","author":"Boillot","year":"2013","journal-title":"J. Chromatogr. A"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.trac.2007.09.010","article-title":"Sample Preparation in Analysis of Pharmaceuticals","volume":"26","author":"Horvat","year":"2007","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.1007\/s00216-015-8617-2","article-title":"Determination of Pharmaceuticals in Bivalves Using Quechers Extraction and Liquid Chromatography-Tandem Mass Spectrometry","volume":"407","author":"Borrull","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_79","first-page":"87","article-title":"Lyophilization\/Freeze Drying\u2014An Review","volume":"3","author":"Nireesha","year":"2013","journal-title":"Int. J. Nov. Trends Pharm. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Takach, E. (2013). Tissue Homogenization. Tissue Analysis for Drug Development, Future Science Ltd.","DOI":"10.4155\/ebo.13.457"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/jssc.201501046","article-title":"Pressurized Liquid Extraction Followed by Liquid Chromatography with Tandem Mass Spectrometry to Determine Pharmaceuticals in Mussels","volume":"39","author":"Borrull","year":"2016","journal-title":"J. Sep. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.trac.2017.09.007","article-title":"Sample Treatment for the Determination of Emerging Organic Contaminants in Aquatic Organisms","volume":"97","author":"Borrull","year":"2017","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Mitra, S. (2003). Sample Preparation Techniques in Analytical Chemistry, John Wiley & Sons, Inc.","DOI":"10.1002\/0471457817"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/jaoac\/86.2.412","article-title":"Fast and Easy Multiresidue Method Employing Acetonitrile Extraction\/Partitioning and \u201cDispersive Solid-Phase Extraction\u201d for the Determination of Pesticide Residues in Produce","volume":"86","author":"Anastassiades","year":"2003","journal-title":"J. AOAC Int."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Lucci, P., Pacetti, D., Nunez, O., and Frega, N. (2012). Current Trends in Sample Treatment Techniques for Environmental and Food Analysis. Chromatography\u2014The Most Versatile Method of Chemical Analysis, IntechOpen Limited.","DOI":"10.5772\/47736"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1080\/10408347.2013.827966","article-title":"Profiling Serotonin Reuptake Inhibitors (SSRIs) in the Environment: Trends in Analytical Methodologies","volume":"44","author":"Silva","year":"2014","journal-title":"Crit. Rev. Anal. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8215271","DOI":"10.1155\/2017\/8215271","article-title":"Dispersive Solid Phase Extraction for the Analysis of Veterinary Drugs Applied to Food Samples: A Review","volume":"2017","author":"Islas","year":"2017","journal-title":"Int. J. Anal. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jhazmat.2016.04.058","article-title":"Lessons Learned from More than Two Decades of Research on Emerging Contaminants in the Environment","volume":"316","author":"Aga","year":"2016","journal-title":"J. Hazard. Mater."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Otles, S. (2012). Methods of Analysis of Food Components and Additives, CRC Press.","DOI":"10.1201\/b11218"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/chromsci\/bmt080","article-title":"HPLC Method for Naproxen Determination in Human Plasma and Its Application to a Pharmacokinetic Study in Turkey","volume":"52","author":"Yilmaz","year":"2014","journal-title":"J. Chromatogr. Sci."},{"key":"ref_91","unstructured":"Ali, J. (2012). Analysis of Non-Steroidal Anti-Inflammatory Drugs Using a Highly Pure, High Surface Area C18 HPLC Column, Thermo Fisher Scientific."},{"key":"ref_92","first-page":"24","article-title":"The Role of Methanol and Acetonitrile as Organic Modifiers in Reversed-Phase Liquid Chromatography","volume":"26","author":"Hopkins","year":"2019","journal-title":"Chromatogr. Today"},{"key":"ref_93","unstructured":"Nemoto, A.C.M. (2019). Monitoring of Anti-Inflammatory Drugs in Hydric Media from Bragan\u00e7a District, Polytechnic Institute of Bragan\u00e7a."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Kazakevich, Y., and LoBrutto, R. (2007). HPLC for Pharmaceutical Scientists, John Wiley & Sons, Inc.","DOI":"10.1002\/0470087951"},{"key":"#cr-split#-ref_95.1","unstructured":"European Commission (2021). Commission Implementing Regulation"},{"key":"#cr-split#-ref_95.2","unstructured":"(EU) 2021\/808 of 22 March 2021 on the Performance of Analytical Methods for Residues of Pharmacologically Active Substances Used in Food-Producing Animals and on the Interpretation of Results as Well as on the Methods To. Off. J. Eur. Union, 180, 84-109."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/6\/415\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:54:18Z","timestamp":1760108058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/6\/415"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,5]]},"references-count":97,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["toxics12060415"],"URL":"https:\/\/doi.org\/10.3390\/toxics12060415","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,5]]}}}