In situ aqueous derivatization and determination of non-steroidal anti-inflammatory drugs by salting-out-assisted liquid–liquid extraction and gas chromatography–mass spectrometry

A new analytical method for the determination of trace levels of five non-steroidal anti-inflammatory drugs (NSAIDs: clofibric acid, ibuprofen, naproxen, diclofenac and ketoprofen) in water samples is described. The analytical procedure involves in situ aqueous derivatization with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) and 2,2,2-trifluoroethylamine hydrochloride (TFEA) and salting-out liquid–liquid extraction (SALLE), followed by gas chromatography–programmed temperature vaporizer–mass spectrometry (GC–PTV–MS). The influence of several parameters on the efficiency of the derivatization (stirring time, reaction time, reagent concentration and pH), and the extraction (solvent, volume, salts and stirring time) and injection steps (liner, injection volume, liner temperature, injection time, venting time and venting flow) was investigated. The detection limits of the method in water varied from 0.042 μg/L for ibuprofen to 1.2 μg/L for ketoprofen. The relative standard deviations (RSD) values were found to be relatively low (<10% for all compounds). The methodology developed was applied to the determination of NSAIDs in several environmental matrices including tap, river, sea and influent and effluent waste water samples. The results obtained show the presence of ibuprofen and naproxen in the influent waste water sample.