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

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.