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. 2017 Sep:183:389-400.
doi: 10.1016/j.chemosphere.2017.05.083. Epub 2017 May 13.

Uptake, biotransformation and elimination of selected pharmaceuticals in a freshwater invertebrate measured using liquid chromatography tandem mass spectrometry

Thomas H Miller  1 , Nicolas R Bury  2 , Stewart F Owen  3 , Leon P Barron  4
Affiliations

Uptake, biotransformation and elimination of selected pharmaceuticals in a freshwater invertebrate measured using liquid chromatography tandem mass spectrometry

Thomas H Miller et al. Chemosphere. 2017 Sep.

Abstract

Methods were developed to assess uptake and elimination kinetics in Gammarus pulex of nine pharmaceuticals (sulfamethazine, carbamazepine, diazepam, temazepam, trimethoprim, warfarin, metoprolol, nifedipine and propranolol) using targeted LC-MS/MS to determine bioconcentration factors (BCFs) using a 96 h toxicokinetic exposure and depuration period. The derived BCFs for these pharmaceuticals did not trigger any regulatory thresholds and ranged from 0 to 73 L kg-1 (sulfamethazine showed no bioconcentration). Metabolism of chemicals can affect accurate BCF determination through parameterisation of the kinetic models. The added selectivity of LC-MS/MS allowed us to develop confirmatory methods to monitor the biotransformation of propranolol, carbamazepine and diazepam in G. pulex. Varying concentrations of the biotransformed products; 4-hydroxypropranolol sulphate, carbamazepine-10,11-epoxide, nordiazepam, oxazepam and temazepam were measured following exposure of the precursor compounds. For diazepam, the biotransformation product nordiazepam was present at higher concentrations than the parent compound at 94 ng g-1 dw. Overall, the results indicate that pharmaceutical accumulation is low in these freshwater amphipods, which can potentially be explained by the rapid biotransformation and excretion.

Keywords: Bioconcentration; Biotransformation; Gammarus pulex; Pharmaceuticals.

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Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Toxicokinetic profiles of selected pharmaceuticals in G. pulex measured using LC-MS/MS. Solid line represents model fit, dashed lines represent 95% confidence interval. (a) carbamazepine, (b) diazepam, (c) metoprolol, (d) nifedipine, (e) propranolol, (f) trimethoprim, (g) temazepam and (h) warfarin.
Fig. 2
Fig. 2
Plots of k1 over time for the selected eight pharmaceuticals.
Fig. 3
Fig. 3
SRM transitions for the detected biotransformed products during toxicokinetic exposures.
Fig. 4
Fig. 4
Determination of biotransformation products (a) Concentration-time profile for propranolol (solid circles) and 4-hydroxypropranolol sulphate (crosses) in G. pulex. (b) Concentration-time profile for diazepam (solid circles), nordiazepam (triangles), oxazepam (squares) and temazepam (crosses) in G. pulex.
See this image and copyright information in PMC

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