Analysis of multi-class pharmaceuticals in fish tissues by ultra-high-performance liquid chromatography tandem mass spectrometry

• Exhaustive method optimization for determination of 20 multi-class pharmaceuticals in fish.
• Method application to different fish tissues.
• In-depth evaluation of several strategies to correct observed matrix effects.
• First monitoring campaing performed in fish in Mediterranean rivers.
• First detection of diclofenac in fish tissues.

A new sensitive method based on pressurized liquid extraction (PLE) and purification by gel permeation chromatography (GPC) prior to ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC–MS/MS) was developed for the determination in fish homogenate, liver and muscle of twenty pharmaceuticals compounds and metabolites from seven commonly used therapeutic families. An extensive matrix effect evaluation was performed in order to select the best approach when analyzing such complex matrices. Limits of detection (MDLs) for the target compounds were in the range of 0.03–0.50 ng/g for fish homogenate, 0.01–0.42 ng/g for fish muscle, and 0.08–0.98 ng/g for fish liver. The method was applied to fish tissues of eleven fish species from four heavily impacted Mediterranean rivers. Nine compounds from five therapeutic families were measured at concentrations higher than MDLs. Highest levels were found in trout liver, with a maximum concentration of 18 ng/g for carbamazepine, whereas the most ubiquitous compound was diclofenac.