## 2 Results and Discussion
### Relationship between Extraction Efficacy and Analyte Characteristics  
This study evaluated thin-film microextraction devices coated with immobilized octadecyl-bonded silica particles. However, silica surfaces can never be entirely bonded with ligands. Due to steric impedance, it is estimated that below half of the silanol groups present on silica surfaces are bonded with octadecylsilane molecules [1], and part of these silanols becomes permanently inaccessible to end-capping agents such as TMS during  
\begin{table}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{**Substance**} & **Extraction Efficacy with 10 μm** & \multicolumn{2}{c}{**Optimal Extraction Conditions**} \\ \cline{2-4}  & **Polar End-Capped Particles and** & & **Stationary Phase +** \\  & **Desorption to DS3a** & **Extraction Efficacy** & **Desorption Solvent** \\ \hline fenoterol & 48.0 (6.7) & 65.1 (2.2) & 45 μm + DS3a \\ carte  
synthesis [34; 35]. This incomplete substitution of silanols causes multiple interactions between the stationary phase (coating) and analytes to affect the extraction efficacy. This phenomenon also explains why no single parameter of the analyte can be perfectly correlated with extraction yield (i.e., [PERSON]'s coefficient of exactly r = 1). Several physicochemical properties of the analytes were selected by the authors as potentially affecting extraction, and the correlation of these parameters with the efficacy of the process was investigated. All physicochemical descriptors used for calculations are available in online databases and are shown in Supplementary Materials Table S4. As expected from a coating prepared with hydrophobic octadecyl-bonded particles, there were two-way significant and strong positive correlations ([PERSON]'s coefficient values of r > 0.5) between the extraction efficacy and hydrophobicity of the analytes. Expressed as the logarithm of the partition coefficient (logP) or the distribution coefficient (logD), the hydrophobicity of the analytes was computed using several programs. logP values were calculated with the ACD/Labs [36], ALOGPS [37; 38], ChemAxon [37; 38], and XlogP3.0 [39] programs. logD values at pH 7.4 were calculated with ACD/Labs [36]. Out of this group of descriptors, logD at pH 7.4 was characterized by the highest correlations with extraction efficacy. Given that logD considers whether the molecule is ionizable or not (and majority of the analytes extracted in this study are), these results are not surprising, and the extractions were performed from PBS, which has a nominal pH value of 7.4. Of the four coatings investigated in this study, one prepared with the 45 um particles exhibits the lowest correlations. The median correlation coefficient value was r = 0.533 (0.495-0.618, \(p\leq 0.005\), \(n=8\)). Greater correlations were observed for smaller particle sizes with median value of r = 0.698 (0.615-0.769, \(p<0.001\), \(n=9\)) for the 10 um particles and r = 0.756 (0.612-0.796, \(p<0.001\), \(n=9\)) for the 5 um particles. The largest correlations occurred with the 10 um particles with polar end-capping with a median value of r = 0.767 (0.646-0.787, \(p<0.001\), \(n=9\)). Stronger correlations were also found in the most efficient desorption solvents, achieving maximum values with the 10 and 45 um particles (both with DS3a) and near-maximum values for the 5 (r = 0.743 in DS1b vs. r = 0.796 in DS1a) and 10 um particles with polar end-capping (r = 0.784 in DS3a vs. r = 0.787 in DS1b). Other investigated analyte parameters included the polar surface area [A\({}^{2}\)], which was computed with ACD/Labs [36], Cactvs 3.4.6.11 [39], and ChemAxon [37; 38] programs; the polarizability [A\({}^{3}\)], which was computed with ACD/Labs [36], and ChemAxon [37; 38]; pKa, which was computed with ChemAxon [37; 38]; and the number of hydrogen acceptor and donor spots, which were computed with ACD/Labs [36], Cactvs 3.4.6.11 [39] and ChemAxon [37; 38].