Magnetic effervescent tablet-assisted ionic liquid dispersive liquid–liquid microextraction employing the response surface method for the preconcentration of basic pharmaceutical drugs: Characterization, method development, and green profile assessment

Abstract

This study demonstrated magnetic effervescent tablet-assisted (META) ionic liquid (IL) dispersive liquid–liquid microextraction (DLLME) as a procedure for extracting pharmaceutical drugs from water samples. An effervescent tablet (ETA) comprising precursors, citric acid and sodium bicarbonate; iron oxide nanoparticles; and IL, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]), was utilized for the dispersion of the extractant in the aqueous phase. A flat-face radius edge tablet was prepared via wet granulation, and its properties were characterized by analyzing its morphology, magnetism, and functional groups. Further, pharmaceutical drugs, namely acetaminophen, atenolol, metoprolol, gliclazide, metformin, lovastatin, nifedipine, and caffeine were utilized as model analytes. Seven variables, namely the tablet weight (1–2 g), the volume of IL (100–500 µL), pH solution adjustment (5–9), the effect of the extraction temperature (15 °C–75 °C), no. of ETAs (2–4 pieces), the effect of the solidification time (3–13 min), and effect of the reconstituting solvent (250–1250 µL), that affected the extraction efficiency were screened and optimized via the Plackett–Burman design (PBD) and central composite design (CCD), respectively. The values of the optimum extraction condition were set, as follows: tablet weight, 1 g; the volume of IL, 500 µL; solution pH, pH 9; extraction temperature, 45 °C; no. of ETAs, 2 pieces; solidification time, 7.5 min; and reconstituting solvent, 750 µL. Combined with high-performance liquid chromatography with diode-array detection (HPLC–DAD) analysis, the developed method demonstrated good linearity (r2 > 0.990), extraction recovery range (75 %–104 %), and detection limits (0.2–6.6 ng mL). The calculated intra- and inter-day precisions, which were expressed as relative standard deviations (RSD, n = 3), were < 10 %. The developed method exhibited greenness, satisfying six green criteria and 0.61 (Analytical GREEnness (AGREE) with metric score).