Bioconcentration and metabolization of pharmaceuticals in marine mussel.
Résumé
The availability of organic contaminants to biota in aquatic environment is assessed firstly through bioaccumulation. Pharmaceuticals accumulate in
freshwater organisms as it has been shown for some of them, mainly in fish species, but also in other model species such as invertebrates and algae. Despite those factors are species-dependent, very few is known in nontarget organisms. In marine organisms, pharmaceuticals have been detected with concentration ranging from ng g-1 d.w. to some thousand ng g-1 d.w. Other hand, it is generally accepted that substances with octanol-water partition coefficient (log Kow) equal to or higher than 3 have the potential to bioaccumulate in biological tissues; but other
factors such as metabolism and the uptake and depuration kinetics must also be taken into consideration. However, studies on pharmaceuticals bioaccumulation in nontarget, marine organisms, determining kinetics for uptake and depuration and taking into consideration metabolites are very scarce. The aim of this work was the determination of bioconcentration, the kinetic constants of uptake and depuration of selected pharmaceutical in Mytilus galloprovincialis. The selected molecules were two benzodiazepines (BZD): diazepam (DZP) and tetrazepam (TZP), and the antiepileptic drug carbamazepine (CBZ). Furthermore, two major metabolites of CBZ were investigated in mussels tissues.Two extraction and
analytical methods were developed for determine the concentration of selected pharmaceutical and the two major metabolites of CBZ at low concentration in mussel tissues. The first one for BZD, consisted of a microwave-assisted extraction and an analysis on a GCMS. The second, for CBZ and the metabolites, was a pressurized liquid extraction and a LCMSMS analysis. The calulated BCFs of the selected pharmaceuticals were 2.2, 50.7 and 99.3 L kg-1 d.w for respectively CBZ, DZP and TZP and increased with logKow (2.3, 2.8 and 3.2, respectively).
This relation was not linear suggesting involvement of other mecanisms than lipohily in bioconcentration. DZP was detected as TZP metabolite. Furthermore, metabolites of CBZ were below the detectable concentrations of 0.7 ng g-1 d.w. in mussels. According to our results, previous described effects of CBZ in mussel should arrive without major CBZ bioconcentration.This late result deserves further research as mussels metabolism should conduct to other more relevant metabolites than those, humans, investigated in this study.