Enantiomeric separation and enantioselective determination of some representive non-steroidal anti-inflammatory drug enantiomers in fish tissues by using chiral liquid chromatography coupled with tandem mass spectrometry

In this work, enantiomeric separation of nine non-steroidal anti-inflammatory drugs including ibuprofen, indoprofen, pranoprofen, flurbiprofen, ketoprofen, carprofen, naproxen, loxoprofen and etodolac was investigated by HPLC combining with four polysaccharide based chiral stationary phases (Chiralpak IA, Chiralpak IB, Chiralpak IC and Chiralpak ID). The effect of various types of the mobile phase, acidic additive types, as well as mobile phase pH on enantiomeric separation was evaluated and optimized in detail. Chiralpak ID showed the best enantioselectivity towards seven of the above nine chiral drugs. Additionally, a sensitive and simple method for simultaneous enantioselective determination of indoprofen, flurbiprofen, carprofen and naproxen enantiomers in fish tissues based on C18 solid phase extraction (SPE) with chiral liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) on Chiralpak ID was established. Method validation showed that good linearity (R-2 > 0.99) for each enantiomer with the limit of quantification in the range of 2-10 ng g(-1) was obtained. Recoveries of the studied profens enantiomers in fish tissues were 82.6% - 106.7% with RSD less than 8.2% at three concentration levels. The proposed method was applied to the real fish samples analysis, providing a reference to fully evaluate the risks of these drug enantiomers in food or environmental samples.