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

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.

A review of the pharmaceutical exposome in aquatic fauna

“…They are, however, pseudo-persistent due to continual influx to the environment from several sources, including waste water treatment plants (WWTPs), manufacturing, agriculture and aquaculture, amongst other routes ( Boxall et al., 2012 ). Furthermore, pharmaceuticals are generally designed not to be bioaccumulative ( Lipinski et al., 1997 ), as demonstrated during in vivo laboratory exposures ( Miller et al, 2016 , 2017 ; Meredith-Williams et al., 2012 ; Nichols et al., 2015 ; Nallani et al., 2011 ). Effects are often studied and observed at non-environmentally relevant concentrations of single compounds (i.e.…”

Role of Hydrophobicity in Bio-Accessibility of Environmental Pollutants Among Different Organisms

“…It is suggested that the bioaccumulation of organic compounds in an aquatic environment is more related to partitioning coefficients than their absolute exposure concentrations. Furthermore, the fate of the environmental contaminants is not only affected mainly by their physio-chemical characteristics, but also biological processes including environmental parameters that play a critical role in the uptake of these chemicals [44][45][46][47]. Biological factors including individual size, life cycle, feeding type, lipid content, respiration strategy, habitat and metabolic processes may affect the uptake and sensitivity of individuals to the contaminants [48][49][50]; however, the available information is still limited [51].…”

A Bayesian framework for estimating parameters of a generic toxicokinetic model for the bioaccumulation of organic chemicals by benthic invertebrates: Proof of concept with PCB153 and two freshwater species

“…Moreover, it has been shown for several aquatic invertebrates, such as the insect Chironomus riparius, that exposure to sediment cannot be ignored (Leppänen and Kukkonen, 1998;Sidney, 2016). The importance of dietary uptake for aquatic invertebrates has been increasingly assessed in recent years (Ashauer 2010, Carrasco-Navarro, 2015Englert, 2017;Miller, 2017;Rösch, 2017). Chironomus sp.…”

“…The simultaneous method estimates both the uptake and elimination rates together, and is considered a potentially more reliable and more realistic model. Only recent studies (Ashauer, 2010;Miller, 2016Miller, , 2017 have applied simultaneous methods for parameter approximation. Sequential or simultaneous methods can be deployed in a frequentist or Bayesian approach.…”