Targeted metabolomics of Gammarus pulex following controlled exposures to selected pharmaceuticals in water.
The effects of pharmaceuticals and personal care products (PPCPs) on aquatic organisms represent a significant current concern. Herein, a targeted metabolomics approach using liquid chromatography-high resolution mass spectrometry (LC-HRMS) is presented to characterise concentration changes in 29 selected metabolites following exposures of aquatic invertebrates, Gammarus pulex, to pharmaceuticals. Method performance revealed excellent linearity (R(2)>0.99), precision (0.1-19%) and lower instrumental limits of detection (0.002-0.20ng) for all metabolites studied. Three pharmaceuticals were selected representing the low, middle and high range of measured acute measured toxicities (of a total of 26 compounds). Gammarids were exposed to both the no-observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) of triclosan (0.1 and 0.3mgL(-1)), nimesulide (0.5 and 1.4mgL(-1)) and propranolol (100 and 153mgL(-1)) over 24h. Quantitative metabolite profiling was then performed. Significant changes in metabolite concentrations relative to controls are presented and display distinct clustered trends for each pharmaceutical. Approximately 37% (triclosan), 33% (nimesulide) and 46% (propranolol) of metabolites showed statistically significant time-related effects. Observed changes are also discussed with respect to internal concentrations of the three pharmaceuticals measured using a method based on pulverised liquid extraction, solid phase extraction and LC-MS/MS. Potential metabolic pathways that may be affected by such exposures are also discussed. This represents the first study focussing on quantitative, targeted metabolomics of this lower trophic level benthic invertebrate that may elucidate biomarkers for future risk assessment.
Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18-26, 08034 Barcelona, Catalonia, Spain; Analytical & Environmental Sciences Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK. Electronic address: cristian.gomez@cid.csic.es.
Cristian
C
Gómez-Canela
Analytical & Environmental Sciences Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Thomas H
TH
Miller
Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Nicolas R
NR
Bury
Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18-26, 08034 Barcelona, Catalonia, Spain.
Romà
R
Tauler
Analytical & Environmental Sciences Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Leon P
LP
Barron
D033304:Amphipoda / Q000502:physiology*; D000818:Animals; D004784:Environmental Monitoring; D005618:Fresh Water; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D052616:Solid Phase Extraction; D014260:Triclosan / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D014874:Water Pollutants, Chemical; D014260:Triclosan
Aquatic toxicology; Gammarus pulex; LC-HRMS; Metabolomics; Pharmaceuticals