Coupling of two centrifugeless ultrasound-assisted dispersive solid/liquid phase microextractions as a highly selective, clean, and efficient method for determination of ultra-trace amounts of non-steroidal anti-inflammatory drugs in complicated matrices.

In this work, a new, simple, rapid, and environmentally friendly method with a high sample clean-up capability termed as centrifugeless ultrasound-assisted dispersive micro solid-phase extraction coupled with salting-out ultrasound-assisted liquid-liquid microextraction based on solidification of a floating organic droplet followed by high performance liquid chromatography is introduced for the first time. In this method, the three non-steroidal anti-inflammatory drugs diclofenac, ibuprofen, and mefenamic acid are first extracted based on an effective nanoadsorbent named as the layered double hydroxide-carbon nanotube nanohybrid. The first step provides a rapid and convenient way to separate the adsorbent from the sample matrix by a syringe nanofilter without additional centrifugation. In the next step, which is based upon the salting-out effect, after emulsification in the presence of ultrasonic irradiation, the phase separation is simply achieved through the salting-out phenomenon, and the extracting solvent is suspended on top of the sample solution. Under the optimal experimental conditions including the initial pH value of 6.0, 8.0 mg of the nanohybrid, 3 min ultrasonic time, 100 μL elution solvent (first step), secondary pH value of 3.0, 60 μL of 1-undecanol, 60 s ultrasonic time, and flow rate of 3 mL min-1 (second step), good responses were obtained for diclofenac, ibuprofen, and mefenamic acid in the concentration ranges of 0.8-2000, 0.8-2500, and 0.5-2000 ng mL-1, respectively, with low limits of detection ranging from 0.1 to 0.2 ng mL-1. The intra-day and inter-day precisions for the target analytes at the three concentration levels were in the ranges of 6.1-7.8% and 6.3-8.1%, respectively. The proposed method was also successfully applied to the biological and waste water samples, and excellent recoveries were obtained in the range of 92.9-103.1% even when the matrix was complex.