Department of Biology, Arsanjan Branch, Islamic Azad University, Arsanjan, Iran.
J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Jun 1;898:24-31. doi: 10.1016/j.jchromb.2012.04.009. Epub 2012 Apr 13.
The present study was focused on the rational development of polymers for selective extraction of allopurinol (ALP) from human plasma. Therefore, a computational modeling approach was combined with the molecular imprinting technology to obtain the polymers. The computational approach was used in order to screen the functional monomers as well as the polymerization solvents for rational design of molecular imprinted polymers (MIPs). It was based on the comparison of the binding energy (ΔE) of the formed complexes between the template molecule and different functional monomers. In the design, the effect of the polymerization solvent was also included using the polarizable continuum model. The theoretical calculation results showed that among virtual solvents tested, acrylamide (AAM) gave the largest ΔE while acrylonitrile (ACN) gave the smallest ΔE in acetone. Therefore, the MIP prepared using AAM as functional monomer in acetone was desired. To examine the validity of this approach, three MIPs were synthesized with different functional monomers i.e. AAM, acrylic acid (AA), and ACN, and then evaluated using Langmuir-Freundlich (LF) isotherm. The results obtained from this experiment confirmed the computational results that the MIP prepared by AAM was the most appropriate adsorbent. Subsequently, the MIP was used to develop a molecular imprinted solid-phase extraction (MISPE) procedure. Finally, the MISPE procedure followed by HPLC was developed for selective extraction and determination of allopurinol in human plasma. For the proposed MISPE method, the linearity between peak area and concentration was found in the range of 0.100-25.000 μM with a linear regression coefficient (R²) of 0.995. The limit of detection (LOD) and quantification (LOQ) in plasma were 0.028 and 0.093 μM, respectively. The results of this study indicated the possibility of using computer aided design for rational selection of functional monomers and solvents for preparation of the MIPs capable of extracting allopurinol from human plasma.
本研究专注于开发聚合物以选择性地从人血浆中提取别嘌醇（ALP）。因此，采用计算建模方法与分子印迹技术相结合来获得聚合物。该计算方法用于筛选功能单体以及聚合溶剂，以实现分子印迹聚合物（MIP）的合理设计。该方法基于比较模板分子与不同功能单体形成的配合物的结合能（ΔE）。在设计中，还使用极化连续体模型考虑了聚合溶剂的影响。理论计算结果表明，在所测试的虚拟溶剂中，丙烯酰胺（AAM）在丙酮中给出最大的ΔE，而丙烯腈（ACN）给出最小的ΔE。因此，希望在丙酮中使用 AAM 作为功能单体制备 MIP。为了检验该方法的有效性，使用不同的功能单体即丙烯酰胺（AAM）、丙烯酸（AA）和丙烯腈（ACN）合成了三个 MIP，并使用 Langmuir-Freundlich（LF）等温线进行了评估。该实验结果证实了计算结果，即由 AAM 制备的 MIP 是最合适的吸附剂。随后，将 MIP 用于开发分子印迹固相萃取（MISPE）程序。最后，开发了 HPLC 后 MISPE 程序，用于选择性提取和测定人血浆中的别嘌醇。对于所提出的 MISPE 方法，在 0.100-25.000 μM 的范围内，峰面积与浓度之间存在线性关系，线性回归系数（R²）为 0.995。在血浆中的检测限（LOD）和定量限（LOQ）分别为 0.028 和 0.093 μM。该研究结果表明，使用计算机辅助设计有可能合理选择功能单体和溶剂来制备能够从人血浆中提取别嘌醇的 MIP。
