Preparation of plastic antibodies for a drug and its metabolites and its application

制备了一种具有亲水性外层修饰的(S)-普萘洛尔和(S)-萘普生分子印迹聚合物（MIP）。首先，以甲基丙烯酸和4-乙烯基吡啶为功能单体，乙二醇二甲基丙烯酸酯为交联剂，采用多步溶胀和热聚合法制备了(S)-普萘洛尔和(S)-萘普生的mip；然后，用单甲基丙烯酸甘油和二甲基丙烯酸甘油1:1的混合物进行亲水性表面改性，在分子印迹开始4小时后直接加入(S)-普萘洛尔和(S)-萘普生的MIPs。与未改性的MIP相比，表面改性的MIP降低了所有溶质的保留因子。然而，表面修饰的MIP和未修饰的MIP均能对外消旋心得安或萘普生进行手性识别。此外，从表面修饰的MIP中可以完全回收牛血清白蛋白。结果表明，(S)-普萘洛尔或(S)-萘普生的手性识别位点在亲水性表面修饰后保持不变，(S)-普萘洛尔或(S)-萘普生的MIP被亲水性外层选择性修饰。结果表明，表面修饰的MIP可用于(S)-普萘洛尔或(S)-萘普生的血清直接注射测定。然而，使用(S)-普萘洛尔-或(S)-萘普生印迹聚合物在低浓度下选择性捕获药物导致了一个严重的问题，因为(S)-普萘洛尔或(S)-萘普生在制备后仍留在MIP内。我们使用结构相关的化合物(S)-pindolol或ibuprofen作为模板制备了MIP。目前，使用MIP同时测定生物体液中的(S)-心得安或(S)-萘普生及其代谢物正在进行中。

A uniform-sized molecularly imprinted polymer (MIP) for (S)-propranolol and (S)-naproxen selectively modified with hydrophilic external layer has been prepared. First, the MIPs for (S)-propranolol and (S)-naproxen were prepared using methacrylic acid and 4-vinylpyridine, respectively, as a functional monomer and ethylene glycol dimethacrylate as a cross-linker by a multi-step swelling and thermal polymerization method. Next, a 1 : 1 mixture of glycerol monomethacrylate and glycerol dimethacrylate was used for hydrophilic surface modification, and it was added directly to the MIPs for (S)-propranolol and (S)-naproxen 4 h after the start of molecular imprinting. The retention factors of all solutes tested were decreased with the surface modified MIP, compared with the unmodified MIP. However, chiral recognition of racemic propranolol or naproxen was attained with the surface modified MIP as well as the unmodified MIP. Further, bovine serum albumin was completely recovered from the surface modified MIP. These results revealed that the chiral recognition sites of (S)-propranolol or (S)-naproxen remained unchanged with hydrophilic surface modification, and that the MIP for (S)-propranolol or (S)-naproxen was selectively modified with hydrophilic external layer. The results reveal that the surface modified MIP could be applicable to direct serum injection assays of (S)-propranolol or (S)-naproxen. However, the use of the (S)-propranolol- or (S)-naproxen-imprinted polymers for the selective trapping at a low concentration of the drug resulted in a serious problem because of elution of (S)-propranolol or (S)-naproxen, which remained within the MIP after preparation. We prepared a MIP using a structurally related compound, (S)-pindolol or ibuprofen, as the template. Now, simultaneous determination of (S)-propranolol or (S)-naproxen and its metabolites in biological fluids using the MIP is in progress.