New robust and efficient liquid membranes for conductive vial electromembrane extraction of acids with low to moderate hydrophilicity in human plasma

Abstract

AbstractThe current paper reports two new, robust, and efficient conditions for electromembrane extraction of acidic substances from human plasma. Two systems were developed based on eutectic solvents: A1 (“A” for acid) comprised dodecyl methyl sulfoxide and thymol in 1:2 ratio (w/w) as liquid membrane, while A2 used [6-methylcoumarin:thymol (1:2)]:2-nitrophenyl octyl ether in 2:1 ratio (w/w). The performance of A1 and A2 was characterized by extraction of 31 acidic model analytes (pharmaceutical drugs and nutrients) spiked into 100 µL human plasma diluted 1:1 (v/v) with phosphate buffer pH 7.4. The acceptor solution was 50 mM NH4HCO3 buffer pH 10.0, and extraction was performed at an agitation rate of 750 RPM. Voltage and extraction time were 30 V for 30 min and 10 V for 20 min for A1 and A2, respectively. Under optimal conditions, A1 extracted analytes with 1.8 ≤ log P ≤ 6.0 with an average recovery (R) of 85.1%, while A2 extracted in a range of 0.5 ≤ log P ≤ 6.0 with an average recovery of 79.9%. Meanwhile, extraction current was low at 9 and 26 µA, respectively, which is indicative of good system robustness. Using UHPLC-MS/MS analysis of the acceptor solution, repeatability of the A1 and A2 methods was determined to be 2.8–7.7% and 3.3–9.4% for R > 40%, matrix effects were 82–117% and 84–112%, respectively, and linear calibration curves were obtained. The performance and compatibility with human plasma represent a major improvement over previous state-of-the-art liquid membranes for acidic analytes, namely 1-octanol. Graphical Abstract