Combination of dispersive solid phase extraction and deep eutectic solvent-based air-assisted liquid-liquid microextraction followed by gas chromatography-mass spectrometry as an efficient analytical method for the quantification of some tricyclic antidepressant drugs in biological fluids.

A dispersive solid phase extraction coupled with deep eutectic solvent-based air-assisted liquid-liquid microextraction has been developed and applied to the extraction and preconcentration of some tricyclic antidepressant drugs in the human urine and plasma samples prior to their determination by gas chromatography-mass spectrometry. In this method, a sorbent (C) is first added into an alkaline aqueous sample and dispersed by vortexing. By this action, the analytes are adsorbed onto the sorbent. Then, the sorbent particles are isolated from the aqueous solution by centrifugation. Afterward, a deep eutectic solvent, prepared from choline chloride and 4-chlorophenol is used to desorb the analytes from the sorbent. Subsequently, the supernatant solution is removed and added into an alkaline deionized water placed into a test tube with a conical bottom. The resulting mixture is rapidly sucked into a glass syringe and then injected into the tube. This procedure is repeated for several times and a cloudy solution consisting of fine droplets of deep eutectic solvent dispersed into the aqueous phase is formed. After centrifuging the obtained cloudy solution, the tiny droplets of the extractant, containing the extracted analytes, settle at the bottom of the tube. Finally, an aliquot of the extractant is taken and injected into the separation system for quantitative analysis. Several significant factors affecting the performance of the proposed method are evaluated and optimized. Under optimum extraction conditions, the method shows low limits of detection in the ranges of 5-10, 8-15 and 32-60 ng L in deionized water, urine, and plasma, respectively. Enrichment factors are observed to be between 325 to 385 in deionized water, 155 to 185 in urine, and 64 to 72 in plasma. Extraction recoveries are in the range of 65-77 (in deionized water), 62-74 (in urine), and 64-72% (in plasma). The relative standard deviations of the proposed method are ≤ 6% for intra- (n = 6) and inter-day (n = 4) precisions at a concentration of 200 ng L of each analyte. Finally, the applicability of the introduced method is investigated by analyzing the selected drugs in different biological fluids. In the proposed method, for the first time, a deep eutectic solvent composed of safe, cheap, and biodegradable compounds was synthesized and used (at μL-level) as an elution and extraction solvent, simultaneously which led to omit the consumption of toxic organic solvents. This represents a significant advantage in the era of green chemistry. In addition, the introduced method is sensitive, simple in operation, rapid, and efficient.