## 2 Materials and Methods
### Molecular Dynamic Simulations  
Molecular dynamics simulation was conducted using a molecular system containing one (1) molecule of template, four (4) or six (6) molecules of functional monomer and twenty (20) molecules of crosslinker in a mixed solvent consisting of isopropanol and methanol (1:1). The number of solvent molecules was in accordance with their density. Two-dimensional structures of SLX, HEMA, EGDMA, TRIM, isopropanol, and methanol were drawn using the ChemBio3D Ultra 12.0 program (Developed by CambridgeSoft Corporation, Cambridge, MA, USA) and then converted into three-dimensional structures using the same program. The ab initio method (Hartree Fock, 3-21 G based set), with Games interface on ChemBio3D Ultra 12.0 was used in the geometry optimization step [39]. PACK-MOL software (version v20.3.3) [40] was used to pack molecules of the pre-polymerization components randomly within a 40 \(\times\) 40 \(\times\) 40 A box with periodic boundary conditions. Molecular dynamics simulations were conducted using the LAMMPS (version 3 Mar 2020 developed by Sandia National Laboratories, Alburquerque, NM, USA) [41] program combined with reax forcefield [42]. The steepest-descent procedure was used in the energy minimization step with maximum iterations of 200,000. This step is performed to let the molecules rearrange and reach the minimum energy, which occurs during the preparation of the actual pre-polymerization mixture. When the minimum energy was reached, an equilibration step of 0.5 ns was used to first simulate a temperature rise from 0 K to 333 K at atmospheric pressure and, second, a constant high temperature at 333 K at atmospheric pressure. This temperature switch was performed to simulate the temperature shift in the real polymerization processes. The NVT ensembles are used in the simulation of molecular systems, with the number of molecules (N), volume (V), and temperature (T) being kept constant in the system. The 1 ns MD simulation in the explicit solvent was carried out at 333 K, while the coordinates and energy were recovered every 1000 steps, with a step time of 0.1 fs. Calculation of non-bonded interactions was done using a 10.0 A cut-off. The Ovito program (version 3.7.4 developed by OVITO GmbH, Darmstadt, Germany) was used to visualize and investigate the molecular structure, a 0.05 A bin size then was employed to calculate the radial distribution function between SLX-HEMA and SLX-crosslinker in the system. Synthesis of Molecularly Imprinted Polymer (MIP) of Salmeterol Xinafate (SLX) and Non-Imprinted Polymer (NIP) Using Precipitation Polymerization  
MIP and NIP were synthesized using the precipitation polymerization method, as follows. MIP was obtained by dissolving SLX (1 mmol) as a template and HEMA as a functional monomer (4 mmol / 6 mmol) in 350 mL of an isopropanol:methanol (1:1) mixture, based on constant associations in a previous study [7] in sealed bottles, and then sonicated for 5 min. Subsequently, EGDMA/TRIM (20 mmol) was added to the solution as a crosslinker and then sonicated for 40 min. Benzoyl peroxide (0.206 mmol) was then added to the vial as the initiator, and the vial was finally placed in a water bath shaker at 70 \({}^{\circ}\)C for 24 h. The polymer formed was then washed with methanol and water. After washing, the polymer was dried in an oven at 60 \({}^{\circ}\)C for 18 h. NIPs were synthesized in the same way, but without the addition of a template, to verify MIP results. The compositions of the synthesized MIP and NIP SLX are presented in Table S1 in Supplementary Materials. The template was removed from the MIP by an ultrasonic extraction method, using 50 mL of a methanol-acetic acid mixture (9:1, \(v/v\)) for 3 h. The polymer was then centrifuged to separate the filtrate. The extracted MIP was then rinsed with 50 mL of the methanol-water mixture (1:1) and dried at 50 \({}^{\circ}\)C for 18 h. The same method was used for NIP, to remove the remaining unreacted reagents.