5 th International Seminar on Pharmaceutical Science and Technology (ISPST)-3rd International Seminar and Expo on Jamu-13th Annual ISCC 2022. | 32 SYNTHESIS OF MOLECULAR IMPRINTED POLYMER SALBUTAMOL USING METHACRYLIC ACID MONOMER AND TRIMETHYL PROPANE TRIMETHACRYLATE (TRIM) AS A CROSS- LINKER THROUGH SUSPENSION POLYMERIZATION Original Article IKE SUSANTI 1 , NISA SAFITRI 1 , RIMADANI PRATIWI 1 , ALIYA NUR HASANAH 1, 2* 1 Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia, 2 Drug Development Study Center, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia * Email: aliya.n.hasanah@unpad.ac.id Received: 01 Sep 2022, Revised and Accepted: 01 Nov 2022 ABSTRACT Objective: This study aims to determine the analytical performances and characteristics of MIP salbutamol made with methacrylic acid (MAA) monomer and trimethylpropane trimethacrylate (TRIM) cross-linker through suspension polymerization. Methods: The MIP salbutamol was synthesized using suspension polymerization. The analytical performances of MIP, such as the adsorption ability, adsorption capacity and selectivity, were evaluated by Spectrophotometer UV-Vis. The physical characterization of MIP and NIP were evaluated using FTIR, TEM-EDS, Brunauer-Emmett-Teller (BET) method and Barret-Joyner-Halenda (BJH) method. Results: Molecular Imprinted Polymer (MIP) showed better analytical performance than Non-Imprinted Polymer (NIP), the adsorption ability of MIP and NIP reached about 90.43% and 53.92%, respectively. The MIP was selective for salbutamol when compared to terbutaline and salmeterol xinafoate with an imprinting factor (IF) of 1.2841. The MIP has spherical shape particles with diameters in the range of 10-100 µm with a surface area of 185.546 m 2 /g, pore volume of 0.257 cm 3 /g, and pore size of 16.599 Å. Conclusion: The Based on these results, MIP salbutamol, has the potential to be developed as a method for the preparation of salbutamol analysis from biological samples. Keywords: Salbutamol, Molecularly imprinted, Suspension polymerization, Separation © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2022.v14s5.01 Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Salbutamol, a beta-2 agonist drug, is a drug used to relieve asthma symptoms by relaxing the muscles that cause the narrowing of the airways to the lungs. This drug is also often used to relieve cough in acute [1]. However, salbutamol is often abused by several parties. Salbutamol has an anabolic effect so the use of oral salbutamol by athletes is feared to be misused as a doping drug or to increase endurance and strength. In 2010, the World Anti-Doping Agency (WADA) added that the use of beta-2 agonist drugs is prohibited except for inhalation of salbutamol with a maximum use of 1600 µg for 24 h. WADA stipulates the maximum level of salbutamol in urine is 1000 ng/ml [2]. Moreover, beta-2 agonist drugs, including salbutamol are also often used illegally to stimulate the growth of meat-producing animals. Residues of beta-2 agonists in the liver and meat of animals are harmful to humans [3]. Therefore, the Indonesian government has banned the use of beta-2 agonist drugs in livestock. This prohibition is stated in the Regulation of the Minister of Agriculture number 14 of 2017 concerning the veterinary drug's classification [4]. From the explanation above, it can be concluded that there is a need for a tool or method that can be used to identify and quantify salbutamol in particular to detect the illegal use of this drug. Several methods have been developed to analyze salbutamol, such as high- performance liquid chromatography (HPLC) [5], liquid chromatography-mass spectrometry (LC-MS) [6], capillary electrophoreses [7], gas chromatography-mass spectrometry (GC-MS) [8], and enzyme immunoassay [9]. However, the instrumentation method shows various weaknesses, one of which is the complicated sample pre-treatment process, especially in separating the target molecule from a complex sample or matrix [10, 11]. Therefore, we need a method that can be a solution to overcome the problems in the pre-treatment process. One method that can be developed is Molecular Imprinted Polymer (MIP). MIP is a polymer synthesized based on the formation of a complementary recognition cavity induced by the template, which is thus made specific in shape, size, and functionality to the target chemical or biological molecule [12]. MIP can be a promising alternative because of its simple synthesis step, high sensitivity and specificity, comparable performance to natural bio-receptors, high stability, and low cost [11]. Several studies used to synthesize salbutamol MIP were bulk polymerization [13] and precipitation polymerization [3]. However, no studies are currently showing the synthesis of salbutamol MIP using suspension polymerization. Suspension polymerization is a polymerization synthesis carried out in a heterophase medium, where the reactive phase (monomer) is insoluble in the continuous phase (usually water). This polymerization is easy and simple to operate; the minimum amount of contaminants in the final product. The particle size ranges obtained from suspension polymerization ranging from 50-500 µm, which can be easily controlled by a combination of stirring speed and suspending agent concentration [14]. Suspension polymerization is also one of the methods that can be applied on a large scale [15]. The factors that influence the result of MIP synthesis besides the polymerization method were the MIP component consisting of templates, functional monomers, cross-linkers, porogens, and initiators [16]. Methacrylic acid was used as a monomer functional because it has a carboxyl group that can act as a hydrogen donor and acceptor simultaneously [17, 18]. This allows a strong interaction between the template and the monomer through hydrogen bonds formed from the hydrogen atom in the–COOH group of methacrylic acid with the oxygen atom in the C=O group of salbutamol [19]. Cross-linker used in this study was TRIM because it provides a polymer with more rigidity and more effective binding sites compared to ethylene glycol dimethacrylate (EGDMA) [20]. The study conducted by Pangkamta et al., (2020) also showed that MIP using TRIM had higher binding than MIP using EGDMA [21]. Therefore, this study aimed to synthesis the MIP salbutamol with methacrylic acid (MAA) monomer and trimethylpropane trimethacrylate (TRIM) cross-linker through suspension polymerization, and determined its analytical performances. International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 14, Special Issue 5, 2022