<p> Electronic Supplementary Material</p><p>Effect of the loading solvent The selectivity of a molecular imprinting polymer is determined by the type of interaction between the monomers and the template, the shape of the cavities, the number of binding sites, and the nature of the solvent present in the synthesis. Most of the molecular imprinting polymers bind the template with hydrogen-bonding, hydrophobic interaction or ionic bonding [11-13]. Initially, this study focused on the ability of imprinted silica gel to specifically recognize estazolam from solutions containing various ratios of organic solvents (methanol or acetonitrile) to water was studied. Imprinted and non-imprinted silica gels, both obtained as described in the experimental section, were evaluated. 2 mL of solution with estazolam at a concentration of 2 mg L-1 was passed through the cartridges. As shown in Fig.1s, the mass of bound estazolam onto imprinted silica gel decreased as the ratio of organic solvent to water increased. This study indicates that the absorption was a combination of the hydrophobic interaction. The estazolam contained several hydrophobic groups, which may strengthen the interaction between the template and the hydrophobic groups (e.g. phenyl, Si-O-Si) grafted onto the activated silica gel when the ratio of water to organic solvent is large. The hydrophobic and porosity effects provided non- selective binding forces for the uptake of estazolam by the imprinted silica gel. For the imprinted silica gel, specific recognition sites formed by the template molecule played an important role in the estazolam binding capacity. This conclusion had also been drawn by Sellergren [14], who stated that the affinity and selectivity of the MIPs were correlated with template hydrophobicity (reflected in the logPOW) in aqueous- rich solution, when the MIP was prepared using prometryn (logPOW =3.4) and atrazine</p><p>(logPOW =2.6) as the template. The binding mass of estazolam onto imprinted silica gel in methanol/water was higher than that in acetonitrile/water at the same ratio of organic solvent to water. Since the imprinted silica gel was prepared in methanol/water, the binding capacity</p><p>1 was better in this medium.</p><p>Fig.S1 The mass of bound estazolam onto the imprinted and non-imprinted silica gel cartridges at different solvent loadings (a: in solution with various ratios of methanol to water; b: in solution with various ratios of acetonitrile to water).</p><p>2</p>