Solid-Phase Extraction of Active Compounds from Natural Products by Molecularly Imprinted Polymers: Synthesis and Extraction Parameters  
[PERSON]  
1 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia (UPM), Sedang 43400, Sedangor, Malaysia; [EMAIL_ADDRESS] (N.M.N. ); [EMAIL_ADDRESS] (S.M.M.F)  
[PERSON]  
1 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia (UPM), Sedang 43400, Sedangor, Malaysia; [EMAIL_ADDRESS] (N.M.N. ); [EMAIL_ADDRESS] (S.M.M.F)  
[PERSON]  
1 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia (UPM), Sedang 43400, Sedangor, Malaysia; [EMAIL_ADDRESS] (N.M.N. ); [EMAIL_ADDRESS] (S.M.M.F)  
[PERSON]  
3 [PERSON]  
Following the review by [PERSON] (2008); [PERSON] (2008) major categories of natural-based source of new active substances (NASs) or new chemical entities (NCEs) as proved by the FDA, dating from January 1981 through 30 th of September 2019, including:  
\"B\": Biological; usually a large (>50 residues) peptide or protein either isolated from an organism/cell line or produced by biotechnological means in a surrogate host  
\"N\": Natural product  
\"NB\": Natural product \"Botanical\" (in general these have been recognized as drug entities by the FDA)  
\"ND\": Derived from a natural product and is usually a semisynthetic modification  
\"S\": Made by total synthesis, but the pharmacophore is/was from a natural product  
A prevailing sentiment in many pharmaceutical organizations is that the search for new bioactive compounds from the natural resources is hampered by the complexity of the work on the natural product extracts, in which the isolation and characterization of bioactive metabolites are challenging ([PERSON] et al., 2017). Since the most often used analytical procedures are costly and time-consuming, determining the most efficient methodologies and strategies is essential to achieving optimum results and cost-effectiveness. Molecularly imprinted polymers (MIPs) are one of the most recently recognized methods for characterizing new types of materials. The identification and separation of various natural compounds is one of the many applications of MIPs. MIPs are stable polymers with specific cavities designed for a particular template molecule, and possesses high selectivity compared to conventional solid phase extraction methods. MIPs are synthetic materials that selectively rebinds a targeted molecule over other closely related compounds via its recognition site. Functional monomers and cross linkers are used to prepare MIPs by polymerizing around a template molecule, resulting in a three-dimensional network polymer with a high cross-link density. In this regard, the interaction ability of the monomer with the template molecule's functional groups are taken into consideration. [PERSON] et al. (2017) describes the mechanism in which the template molecule is removed after polymerization, and subsequently, binding sites with similar shape, size, and functionality to the target analyte are generated. This results in an imprinted polymer that is stable, robust, and resistant to a wide range of pH, solvents and temperature. Thus, MIPs behave similarly to natural receptor interactions in which a target molecule (i.e., antibody-antigen) is selectively retained, minus the associated stability limitations. Research in the field of MIPs has gotten much attention, as shown in Figure 1, due to their advantages such as their convenient and straightforward preparation, predetermined selectivity, and robustness in organic solvents--acidic or basic reagents, and durability in high temperatures. To prepare MIPs, a functional monomer and crosslinker in the presence of a template are utilized. The template-monomer system is chosen so that the imprint molecule is able to forms a complex in solution with numerous functional monomers. The resulting imprints have steric (size and shape) and chemical (spatial arrangement of complementary functionality) memory of the template.