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A robust extraction method against the variations of sample ionic strength viz. ionic liquid-based ultrasound-assisted  in situ  solvent formation microextraction (IL-UA-ISFME) was coupled for the first time with high-performance liquid chromatography–ultraviolet detection (HPLC–UV), and successfully used as a more sustainable approach for the determination of meloxicam (MEL) in human plasma. Herein, a hydrophobic IL (1-butyl-3-methylimidazolium hexafluorophosphate) was formed by adding a hydrophilic IL (1-butyl-3-methylimidazolium tetrafluoroborate) to aqueous sample solution containing an ion-exchange reagent (sodium hexafluorophosphate). The target analyte was transferred into the IL medium while the extraction solvent was completely dispersed into the sample using ultrasonic irradiation and then, the settled enriched phase was injected to HPLC. Firstly, main factors affecting the microextraction performance were evaluated and optimized. The linearity was in the range of 5–1,500 ng mL −1  with regression coefficient corresponding to 0.997. Limits of detection (LOD; signal-to-noise ratio ( S / N ) = 3) and quantification (LOQ,  S / N  = 10) were 1 and 5 ng mL −1 , respectively. An acceptable recovery range of 82.1–93.6% and satisfactory intra-assay (3.6–4.8%,  n  = 6) and inter-assay (3.3–5.1%,  n  = 9) precision as well as remarkable sample clean up exhibited good efficiency of the method. The freeze-thaw stability study was performed for samples and standard solutions. To study the applicability of the proposed method, it was employed for the determination of MEL in human plasma after oral administration of the drug and some pharmacokinetic data were achieved. The technique proved to be accurate and reliable for the screening intentions.

journal of chromatographic science

Quantification of Meloxicam in Human Plasma Using Ionic Liquid-Based Ultrasound-Assisted  In Situ  Solvent Formation Microextraction Followed by High-Performance Liquid Chromatography