Development of sensitive and selective method for the determination of drugs and their metabolites in biological fluids using artificial antibodies

开发使用人工抗体测定生物体液中药物及其代谢物的灵敏和选择性方法

• 批准号: 12672099
• 负责人: HAGINAKA Jun
• 金额: $ 0.77万
• 依托单位: Mukogawa Women's University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672099/
• 关键词: artificial antibody; molecular imprinting; biological fluids; propranolol; naproxen; atenolol; alprenolol; ibuprofen; ピンドロール; 分子インプリント

First, the MIPs for 2-arylpropionic acid derivative and p-blocker were prepared using 4-VPY and MAA, respectively, as functional monomers by a multi-step swelling and thermal polymerization method. Next, a 1 : 1 mixture of GMMA and GDMA was used for hydrophilic surface modification, and it was added directly to the MIP for the drug 4 h after the start of molecular imprinting. The results revealed that the molecular recognition sites of the target drug remained unchanged with hydrophilic surface modification.Further, after hydrophilic surface modification of the MIP, bovine serum albumin was almost completely recovered from the RAM-MIP. The results described above reveal that the MIP for 2-arylpropionic acid derivative or P-blocker is selectively modified with hydrophilic external layer, and that direct serum injection assays of the drug could be attained using the RAM-MIP. The obtained RAM-MIP for 2arylpropionic acid derivative or p-blocker was applied for direct serum injection assays of the drug by column-switching system, consisting of a RAM-MIP and a conventional CI S-silica column. However, leakage of the imprint molecule prevented accurate and precise assays of the drug. This problem has been overcome by using the RAM-MIP for a structurally related compound. The developed method should have wide applicability for the determination of a drug in biological fluids

首先，分别以4-VPY和MAA为功能单体，通过多步溶胀和热聚合方法制备了2-芳基丙酸衍生物和β-阻断剂的MIPs。接下来，一个1：1的GMMA和GDMA的混合物用于亲水性表面修饰，并且在分子印迹开始后4 h将其直接添加到用于药物的MIP中。结果表明，经亲水性表面修饰后，目标药物的分子识别位点基本不变，而牛血清白蛋白经亲水性表面修饰后几乎完全从RAM-MIP中回收。上述结果表明，2-芳基丙酸衍生物或P-阻断剂的MIP被亲水性外层选择性地修饰，并且使用RAM-MIP可以实现药物的直接血清注射测定。将所获得的2-芳基丙酸衍生物或β-受体阻滞剂的RAM-MIP应用于由RAM-MIP和常规CIS-硅胶柱组成的柱切换系统中的药物的直接血清注射测定。然而，印记分子的泄漏阻碍了药物的准确和精确的测定。这个问题已经通过使用结构相关化合物的RAM-MIP克服。所开发的方法应具有广泛的适用性，用于测定生物体液中的药物

项目成果

Jun Haginaka: "Uniform-sized molecularly imprinted polymers for 2-arylpropionic acid derivatives selectively modified with hydrophilic external layer and their applications to direct serum injection analysis"Anal.Chem.. 72. 5206-5210 (2000)

Jun Haginaka：“用亲水性外层选择性修饰的 2-芳基丙酸衍生物的均一尺寸分子印迹聚合物及其在直接血清注射分析中的应用”Anal.Chem.. 72. 5206-5210 (2000)

Jun Haginaka: "Uniform-sized molecularly imprinted polymer for (S)-propranolol"J.Pharm.Biomed.Anal.. 22. 899-907 (2000)

Jun Haginaka：“(S)-普萘洛尔的均一尺寸分子印迹聚合物”J.Pharm.Biomed.Anal.. 22. 899-907 (2000)

Jun Haginaka: "HPLC-based bioseparations using molecularly imprinted polymers"Bioseparation. (in press)

Jun Haginaka：“使用分子印迹聚合物进行基于 HPLC 的生物分离”生物分离。

Jun Haginaka and Chino Kagawa: "Uniformlv sized molecularlv imorinted polymer for (S)-chlorpheniramine : Evaluation of retention and molecular recognition properties in aqueous mobile phase"J. Chromatogr. A.. 948. 77-84 (2002)

Jun Haginaka 和 Chino Kakawa：“用于 (S)-扑尔敏的均一尺寸分子嵌合聚合物：水性流动相中保留和分子识别特性的评估”J。

Jun Haginaka: "HPLC-based bioseparations using molecularly imprinted polymers"BioSeparation. (In press). (2002)

Jun Haginaka：“使用分子印迹聚合物进行基于 HPLC 的生物分离”BioSeparation。