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，通过多步肿胀和热聚合方法，分别使用4-VPY和MAA作为功能单体制备了2-芳基丙酸衍生物和P-Blocker的MIP。接下来，将GMMA和GDMA的1：1混合物用于亲水性表面修饰，并在分子印刷开始后4小时将其直接添加到MIP中。结果表明，目标药物的分子识别位点与亲水性表面的修饰保持不变。在MIP的亲水性表面修饰后，牛血清白蛋白几乎完全从RAM-MIP中完全回收。上述结果表明，用亲水性外层选择性地修饰了2-芳基丙酸衍生物或P-阻滞剂的MIP，并且可以使用RAM-MIP来获得该药物的直接血清注射测定法。通过柱切换系统将获得的2级丙酸衍生物或P-blocker获得的RAM-MIP用于对药物进行直接血清注射测定法，该测定系统由RAM-MIP和常规CI S-Silica柱组成。但是，烙印分子的泄漏阻止了对药物的准确和精确测定。通过将RAM-MIP用于结构相关的化合物，已经克服了此问题。开发的方法应具有广泛的适用性，以确定在生物流体中的药物

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: "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: "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). (2002)

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

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。