Detection of naproxen and its metabolites in fish bile following intraperitoneal and aqueous exposure.
OBJECTIVE
The anti-inflammatory drug naproxen (NPX) has been found as a micropollutant in river water downstream the discharge points of wastewater treatment plants (WWTP). In this study, rainbow trout (Oncorhynchus mykiss) was exposed to NXP and the uptake and metabolism of the drug was studied.


METHODS
Following exposure through intraperitoneal injection (i.p., 0.5 mg NPX/100 g fish biomass) and through water (1.6 μg L(-1)), the bile was collected and analyzed with various LC-MS/MS methods. The identification of the formed metabolites in i.p. injected fish 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 an ion trap mass analyzer (IT-MS).


RESULTS
No matter the exposure route, the main metabolites were found to be acyl glucuronides of NPX and of 6-O-desmethylnaproxen. Also, unmetabolized NPX was detected in the bile. The total bioconcentration factors (BCF(total-bile)) of NPX and the metabolites in the bile of fish exposed through water ranged from 500 to 2,300.


CONCLUSIONS
The findings suggest that fish living downstream WWTPs may take up NPX and metabolize the compound. Consequently, NPX and its metabolites in bile can be used to monitor the exposure of fish to NPX.
Laboratory of Organic Chemistry, Åbo Akademi University, Biskopsgatan 8, 20500, Åbo/Turku, Finland.
Jenny-Maria
JM
Brozinski
Marja
M
Lahti
Aimo
A
Oikari
Leif
L
Kronberg
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001682:Biological Availability; D004781:Environmental Exposure; D007274:Injections, Intraperitoneal; D015394:Molecular Structure; D009288:Naproxen / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014874:Water Pollutants, Chemical; D009288:Naproxen
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