###### Abstract  
The rational preparation of molecularly imprinted polymers (MIPs) in order to have selective extraction of salmeterol xinafoate (SLX) from serum was studied. SLX is an acting \(\beta\)-adrenergic receptor agonist used in the treatment of asthma and has an athletic performance-enhancing effect. Molecular dynamics were used for the simulation of the SLX-imprinted pre-polymerization system, to determine the stability of the system. The computational simulation showed that SLX as a template, 4-hydroxyethyl methacrylate (HEMA) as a monomer, and trimethylolpropane trimethacrylate (TRIM) as a crosslinker in mol ratio of 1:6:20 had the strongest interaction in terms of the radial distribution functional. To validate the computational result, four polymers were synthesized using the precipitation polymerization method, and MIP with composition and ratio corresponding with the system with the strongest interaction as an MD simulation result showed the best performance, with a recovery of 96.59 \(\pm\) 2.24% of SLX in spiked serum and 92.25 \(\pm\) 1.12% when SLX was spiked with another analogue structure. Compared with the standard solid phase extraction sorbent C-18, which had a recovery of 79.11 \(\pm\) 2.96%, the MIP showed better performance. The harmony between the simulation and experimental results illustrates that the molecular dynamic simulations had a significant role in the study and development of the MIPs for analysis of SLX in biological fluid. s 2022  
porous material with complementary binding features concerning the molecule's structure, shape, and spatial orientation [8]. As a smart synthetic material, MIP is extensively used in numerous areas including sensors, chromatography, drug delivery systems, and environmental separations/analysis [9]. The application of MIPs is particularly used in solid phase extraction [10; 11; 12] and, moreover, it is used in analytical columns in chromatography [13; 14; 15] and as a film layer in sensors [16; 17; 18]. It is known that the selective recognition of MIP-ligand comes from the interaction between the template and the functional monomer present in the pre-polymerization solution [19]. Therefore, the molecular interaction mechanisms that exist during the pre-polymerization stage can be used as a prognostic tool for polymer performance [20]. Affinity of template molecules can be improved by selecting an appropriate functional monomer. This selection can reduce the non-specific interaction happening in MIPs and enhance the specific recognition of MIPs to the template molecule [21]. The choice of crosslinker is another crucial step in the construction of selective polymer systems [22]. The stability of the interaction between the template and the crosslinker should be weak [23]. The crosslinker may compete with the functional monomer, which may result in the MIPs having poor recognition properties with respect to the targeted molecules [24]. There are some crosslinkers that could be used in the synthesis of MIP, including ethylene glycol dimethacrylate (EGDMA) [25], trimethylolpropane trimethacrylate (TRIM) [26], piperazine diacrylamide (PDA) [27], (+)-\(N\),\(N^{\prime}\)-diallytartadiamide (DATD) [28], methylenediacrylamide (MBAA) [29], diisopropylbenzene [30], bisacryloylamidopyridine [31], \(N\),\(O\)-bismethacryloyl ethanolamine (NOBE) [32], glycidyl methacrylate (GMA) [33], and divinylbenzene (DVB) [34]. Synthesizing MIP relying on experimental trial and error will be very time-consuming and resource-consuming [35]. Nowadays, a computational approach is already used extensively to investigate the design and synthesis of MIP to give MIPs with excellent molecular recognition ability [36]. In a previous study [7], the molecular modeling approach and bulk polymerization method were employed to design and synthesize MIP for the analysis of SLX from spiked serum.