Rapid analysis of non-steroidal anti-inflammatory drugs in tap water and drinks by ionic liquid dispersive liquid–liquid microextraction coupled to ultra-high performance supercritical fluid chromatography

Abstract

A novel rapid analytical method for the determination of four non-steroidal anti-inflammatory drugs (NSAIDs) – nabumetone, ibuprofen, naproxen and diclofenac – in tap water and drinks is presented. The method is based on ultrasound-assisted ionic liquid dispersive liquid–liquid microextraction (US-IL-DLLME) followed by ultra-high performance supercritical fluid chromatography (UHPSFC) coupled to a photo-diode array detector (PDA). The ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate ([C₈MIM][PF₆]) and methanol were used as the extraction and dispersion solvents for the DLLME procedure other than using a toxic chlorinated solvent. Plackett–Burman and Box–Behnken designs were applied as the experimental design strategies to screen and optimize the experimental variables such as the volume of the ionic liquid, the volume of the disperser solvent, sample pH, ionic strength, ultrasonication time and centrifugation time which affected the extraction efficiency. Separation conditions of UHPSFC, such as column screening, modifiers, column temperature, back pressure and flow rate, were also optimized in this study. 4 NSAIDs were simultaneously separated and determined in 2.1 minutes. The optimized US-IL-DLLME-UHPSFC-PDA method showed good enrichment factors (126–132) and recoveries (81.37–107.47%) for the rapid extraction of nabumetone, ibuprofen, naproxen and diclofenac in tap water and drinks. The method's limits of detection for nabumetone, ibuprofen, naproxen and diclofenac were 1.56, 7.69, 0.62, and 7.37 ng mL⁻¹ with excellent linearity (R > 0.9957).