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      A review of the pharmaceutical exposome in aquatic fauna

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          Abstract

          Pharmaceuticals have been considered ‘contaminants of emerging concern’ for more than 20 years. In that time, many laboratory studies have sought to identify hazard and assess risk in the aquatic environment, whilst field studies have searched for targeted candidates and occurrence trends using advanced analytical techniques. However, a lack of a systematic approach to the detection and quantification of pharmaceuticals has provided a fragmented literature of serendipitous approaches. Evaluation of the extent of the risk for the plethora of human and veterinary pharmaceuticals available requires the reliable measurement of trace levels of contaminants across different environmental compartments (water, sediment, biota - of which biota has been largely neglected). The focus on pharmaceutical concentrations in surface waters and other exposure media have therefore limited both the characterisation of the exposome in aquatic wildlife and the understanding of cause and effect relationships. Here, we compile the current analytical approaches and available occurrence and accumulation data in biota to review the current state of research in the field. Our analysis provides evidence in support of the ‘Matthew Effect’ and raises critical questions about the use of targeted analyte lists for biomonitoring. We provide six recommendations to stimulate and improve future research avenues.

          Graphical abstract

          Highlights

          • Occurrence and accumulation of pharmaceuticals in aquatic fauna is presented.

          • Evidence of the Matthew Effect from biased pharmaceutical pre-selection.

          • Field versus laboratory derived accumulation factors showed a large disparity.

          • Specific accumulation is pronounced for liver and bile over other tissues.

          • Recommendations for advancements within environmental toxicology are proposed.

          Abstract

          The determination of the pharmaceutical exposome in aquatic fauna is critical to understanding the extent of contamination and the potential risk in the environment.

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          Most cited references178

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          Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS.

          In recent years, high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) detection has been demonstrated to be a powerful technique for the quantitative determination of drugs and metabolites in biological fluids. However, the common and early perception that utilization of HPLC-MS/MS practically guarantees selectivity is being challenged by a number of reported examples of lack of selectivity due to ion suppression or enhancement caused by the sample matrix and interferences from metabolites. In light of these serious method liabilities, questions about how to develop and validate reliable HPLC-MS/MS methods, especially for supporting long-term human pharmacokinetic studies, are being raised. The central issue is what experiments, in addition to the validation data usually provided for the conventional bioanalytical methods, need to be conducted to confirm HPLC-MS/MS assay selectivity and reliability. The current regulatory requirements include the need for the assessment and elimination of the matrix effect in the bioanalytical methods, but the experimental procedures necessary to assess the matrix effect are not detailed. Practical, experimental approaches for studying, identifying, and eliminating the effect of matrix on the results of quantitative analyses by HPLC-MS/MS are described in this paper. Using as an example a set of validation experiments performed for one of our investigational new drug candidates, the concepts of the quantitative assessment of the "absolute" versus "relative" matrix effect are introduced. In addition, experiments for the determination of, the "true" recovery of analytes using HPLC-MS/MS are described eliminating the uncertainty about the effect of matrix on the determination of this commonly measured method parameter. Determination of the matrix effect allows the assessment of the reliability and selectivity of an existing HPLC-MS/MS method. If the results of these studies are not satisfactory, the parameters determined may provide a guide to what changes in the method need to be made to improve assay selectivity. In addition, a direct comparison of the extent of the matrix effect using two different interfaces (a heated nebulizer, HN, and ion spray, ISP) under otherwise the same sample preparation and chromatographic conditions was made. It was demonstrated that, for the investigational drug under study, the matrix effect was clearly observed when ISP interface was utilized but it was absent when the HN interface was employed.
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            Pharmaceuticals and personal care products in the environment: agents of subtle change?

            During the last three decades, the impact of chemical pollution has focused almost exclusively on the conventional "priority" pollutants, especially those acutely toxic/carcinogenic pesticides and industrial intermediates displaying persistence in the environment. This spectrum of chemicals, however, is only one piece of the larger puzzle in "holistic" risk assessment. Another diverse group of bioactive chemicals receiving comparatively little attention as potential environmental pollutants includes the pharmaceuticals and active ingredients in personal care products (in this review collectively termed PPCPs), both human and veterinary, including not just prescription drugs and biologics, but also diagnostic agents, "nutraceuticals," fragrances, sun-screen agents, and numerous others. These compounds and their bioactive metabolites can be continually introduced to the aquatic environment as complex mixtures via a number of routes but primarily by both untreated and treated sewage. Aquatic pollution is particularly troublesome because aquatic organisms are captive to continual life-cycle, multigenerational exposure. The possibility for continual but undetectable or unnoticed effects on aquatic organisms is particularly worrisome because effects could accumulate so slowly that major change goes undetected until the cumulative level of these effects finally cascades to irreversible change--change that would otherwise be attributed to natural adaptation or ecologic succession. As opposed to the conventional, persistent priority pollutants, PPCPs need not be persistent if they are continually introduced to surface waters, even at low parts-per-trillion/parts-per-billion concentrations (ng-microg/L). Even though some PPCPs are extremely persistent and introduced to the environment in very high quantities and perhaps have already gained ubiquity worldwide, others could act as if they were persistent, simply because their continual infusion into the aquatic environment serves to sustain perpetual life-cycle exposures for aquatic organisms. This review attempts to synthesize the literature on environmental origin, distribution/occurrence, and effects and to catalyze a more focused discussion in the environmental science community.
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              Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data

              The occurrence and fate of pharmaceutically active compounds (PhACs) in the aquatic environment has been recognized as one of the emerging issues in environmental chemistry. In some investigations carried out in Austria, Brazil, Canada, Croatia, England, Germany, Greece, Italy, Spain, Switzerland, The Netherlands, and the U.S., more than 80 compounds, pharmaceuticals and several drug metabolites, have been detected in the aquatic environment. Several PhACs from various prescription classes have been found at concentrations up to the microg/l-level in sewage influent and effluent samples and also in several surface waters located downstream from municipal sewage treatment plants (STPs). The studies show that some PhACs originating from human therapy are not eliminated completely in the municipal STPs and are, thus, discharged as contaminants into the receiving waters. Under recharge conditions, polar PhACs such as clofibric acid, carbamazepine, primidone or iodinated contrast agents can leach through the subsoil and have also been detected in several groundwater samples in Germany. Positive findings of PhACs have, however, also been reported in groundwater contaminated by landfill leachates or manufacturing residues. To date, only in a few cases PhACs have also been detected at trace-levels in drinking water samples.
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                Author and article information

                Contributors
                Journal
                Environ Pollut
                Environ. Pollut
                Environmental Pollution (Barking, Essex : 1987)
                Elsevier Applied Science Publishers
                0269-7491
                1873-6424
                1 August 2018
                August 2018
                : 239
                : 129-146
                Affiliations
                [a ]Analytical & Environmental Sciences Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London, SE1 9NH, United Kingdom
                [b ]Faculty of Science, Health and Technology, University of Suffolk, James Hehir Building, University Avenue, Ipswich, Suffolk, IP3 0FS, UK
                [c ]Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
                [d ]AstraZeneca, Global Environment, Alderley Park, Macclesfield, Cheshire SK10 4TF, UK
                [e ]Metabolomics Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK
                Author notes
                []Corresponding author. Analytical & Environmental Sciences Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London, SE1 9NH, United Kingdom. thomas.miller@ 123456kcl.ac.uk
                Article
                S0269-7491(17)35237-5
                10.1016/j.envpol.2018.04.012
                5981000
                29653304
                19026235-07d4-4bee-a95c-3d853718c86b
                © 2018 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 December 2017
                : 26 March 2018
                : 2 April 2018
                Categories
                Article

                General environmental science
                occurrence,pharmaceuticals,fish,bioconcentration,invertebrates
                General environmental science
                occurrence, pharmaceuticals, fish, bioconcentration, invertebrates

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