Identification and dose dependency of ibuprofen biliary metabolites in rainbow trout

Abstract

The biotransformation of the anti-inflammatory drug ibuprofen (IBF) was studied by exposing rainbow trout (Oncorhynchus mykiss) to IBF via intraperitoneal (i.p.) injection, and via water at four (0.17, 1.9, 13 and 145 μg L(-1)) exposure levels for 4d. Following exposure, the bile was collected and analyzed by LC-MS/MS methods. The identification of the formed metabolites in i.p. injected fish bile was based on the exact mass determinations by a time-of-flight mass analyzer (Q-TOF-MS) and on the studies of fragments and fragmentation patterns of precursor ions by ion trap mass analyzer (IT-MS). In addition to unmetabolized IBF, several phase I and phase II metabolites were found in the bile. The main metabolites were acyl glucuronides and taurine conjugates of IBF and of hydroxylated IBFs. The bioconcentration factors (BCFbile), defined as the ratio of the sum of IBF and its metabolites in fish bile to the concentration of IBF in water, was determined following enzymatic deconjugation and was found to range from 14000 to 49000. The highest BCFbile was found at the lowest exposure concentration (0.17 μg L(-1)). The results show that rainbow trout has a high capacity for biotransformation of IBF, and the exposure of fish to sub μg L(-1) concentrations of IBF can be determined by the analyses of the biliary metabolites of the compound.

Keywords: Biotransformation; Ibuprofen; Metabolites; Pharmaceutical; Rainbow trout.