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.
Highlights
For precise analysis of biota like G. pulex for trace pharmaceutical residue determination, it is recommended that stable isotope labelled internal standard (SIL-IS) be used with liquid chromatography (LC)-mass spectrometry (MS)/MS to overcome precision problems relating to the limited sample mass available and to enable the number of specimens to be minimised
As an alternative to traditional liquid scintillation counting (LSC) approaches, LC-MS/MS was shown as a suitable technique for the measurement of uptake and elimination kinetics
Sulfamethazine showed no bioconcentration in the animals, as no peaks were detected upon exposure
Summary
Uptake was mainly considered to occur by passive diffusion across cellular membranes and traditional models relied heavily on physico-chemical properties such as octanol-water partition coefficients (logP) to describe and predict xenobiotic concentrations in biota (Kanazawa, 1981; Neely et al, 1974; Veith et al, 1979) Such earlier works often focussed on neutral compounds (Fu et al, 2009; Klosterhaus et al, 2013; Wu et al, 2013), but more recently identified micropollutant classes, such as pharmaceuticals, are somewhat different in that they are often ionisable and have a wider range of molecular polarity. As most of the reported work has focussed on vertebrates such as fish (Gobas et al, 1986; Kanazawa, 1981; Spacie and Hamelink, 1982; Veith et al, 1979), the bioaccumulation of compounds in invertebrates is not well understood
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