The analytical proficiency of the optimized systems, A1 and A2, was subsequently evaluated. This was not intended as a full validation but aimed to demonstrate their basic analytical merits. The results are summarized in Figure and additionally provided in Table . Both systems extracted all model analytes within 1.0 ≤ log P ≤ 5.3 with greater than 40% recovery, except for kynurenic acid (log P = 1.87). Additionally, a few more hydrophilic analytes such as enalapril (log P = 0.59), piroxicam (log P = 0.39), and nicotinic acid (log P = -0.50) were extracted with high efficiency. For log P > 2.3, the extraction efficiency of A1 and A2 was identical. However, system A2 was more efficient for log P < 2.3, with most notable difference observed for kynurenic acid (log P = 1.87, R = 8.5%/35.7% for A1/A2), furosemide (log P = 1.75, R = 69.1%/91.2% for A1/A2), 3-indoleacetic acid (log P = 1.71, R = 65.2%/96.8% for A1/A2), and nicotinic acid (log P = -0.50, R = 32.2%/80.0% for A1/A2). The difference is explained by the lower hydrophobicity of 6-methylcoumarin (log P = 2.3) compared to DDMS (log P = 3.6). For analytes with R > 40%, the repeatability was 2.8-7.7% and 3.3-9.4% for system A1 and A2 (Figure ), respectively, and both systems were thus in agreement with criterion 7. Figure shows the linearity of extracted calibration curves, with most r 2 >0.9900 for R > 40% and several with lower recovery. Exceptions to this were nicotinic acid (r 2 = 0.9609 and R = 80.0%) and 3-indoleacetic acid (r 2 = 0.8868 and R = 96.8%) in system A2. Matrix effect during LC-MS analysis was studied for all model analytes and covered the entire span of the LC elution gradient. As seen from the violin distribution plots in Figure , no major matrix effects were observed in either system, which indicated good clean-up of the plasma matrix. The current during extraction was stable (Figure ) in both systems and below the defined acceptance criterium of 50 µA. System stability was also evaluated by the dissolution of liquid membrane components into the acceptor phase during extraction, by measuring the individual components with LC-UV. The overall loss of liquid membrane to the acceptor phase was 1.069% ± 0.005 and 0.886% ± 0.037 for system A1 and A2, respectively, which was considered acceptable and clearly did not cause any disturbance in LC-MS signals (no matrix effects). The contribution from individual components is shown in Figure . Previously developed generic systems for bases, B1, B2, and B3 have combined extraction windows from -2.0 ≤ log P ≤ 6.4, but are not suitable for extraction of acids. Systems A1 and A2 both, however, feature HBA and dipole interaction that are favorable for EME of bases, and were therefore briefly tested using a previously reported set of 90 bases (-4.2 ≤ log P ≤ 8.1) and associated UHPLC-MS/MS method . For this, plasma samples were adjusted to pH 2.4 using formic acid, while the acceptor was 100 mM formic acid. All other parameters were as indicated in Table . The results are summarized in Figure . System A1 extracted within a window of 0.8 ≤ log P ≤ 4.2 with an average recovery of 74.3%, while the window for system A2 was 0.4 ≤ log P ≤ 3.7 with an average recovery of 68.7%. System A2 however also extracted several bases with log P < 0 with high efficiency. System A1 and A2 may therefore also be alternatives to the previously proposed B1 and B2 systems.