State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
Suzhou CretBiotech Ltd., 99 Jinji Lake Avenue, Suzhou, 215123 PR China.
J Food Drug Anal. 2024 Mar 15;32(1):65-78. doi: 10.38212/2224-6614.3493.
Aristolochic acid nephropathy (AAN) has drawn increasing public attention. Organic anion transporters (OATs) are considered to be responsible for mediating nephrotoxicity of aristolochic acids (AAs), as AAs are typical OAT1 substrates that exhibit anionic properties and contain one hydrophobic domain. Inspired by the OAT1 three-dimensional structure or substrate/protein interactions involved in transport, we designed a magnetic polymeric hybrid, mimicking the effect of basic and aromatic residues of OAT1, for efficient enriching aristolochic acid I (AA I) and aristolochic acid II (AA II) in Traditional Chinese patent medicines (TCPM). N, N-dimethylaminopropyl acrylamide (DMAPAm) was used as a cationic monomer and copolymerized with divinylbenzene (DVB) onto the surface of monodisperse magnetic nanoparticles (denoted as MNs@SiOT-DvbDam). The magnetic polymer hybrid demonstrated high selectivity and capacity for AAs, which was mainly attributed to (1) electrostatic interactions from the cationic or basic moiety of DMAPAm and (2) the hydrophobic and π-π stacking interactions from the aromatic ring of DVB. Additionally, the surface of the hybrid exhibited amphiphilic property according to the ionization of DMAPAm, thus improving the compatibility of the adsorbent with the aqueous sample matrix. This strategy was proven to be robust in the analysis of real drug samples, which was characterized by a good linearity, high recovery and satisfactory reusability. This work confirmed that the proposed tool could be a promising candidate for enhancing the extraction selectivity of AAs in Traditional Chinese medicines (TCM).
马兜铃酸肾病（AAN）越来越受到公众关注。有机阴离子转运体（OATs）被认为负责介导马兜铃酸（AAs）的肾毒性，因为 AAs 是典型的 OAT1 底物，具有阴离子特性并含有一个疏水区。受 OAT1 三维结构或参与转运的底物/蛋白相互作用的启发，我们设计了一种磁性聚合物杂化物，模拟 OAT1 的碱性和芳香族残基的作用，用于高效富集中药专利药（TCPM）中的马兜铃酸 I（AA I）和马兜铃酸 II（AA II）。N，N-二甲基丙烯酰胺（DMAPAm）用作阳离子单体，并与二乙烯基苯（DVB）共聚到单分散磁性纳米颗粒（表示为 MNs@SiOT-DvbDam）的表面上。磁性聚合物杂化物对 AAs 表现出高选择性和高容量，这主要归因于（1）DMAPAm 的阳离子或碱性部分的静电相互作用，和（2）DVB 的芳香环的疏水和π-π堆积相互作用。此外，根据 DMAPAm 的离子化，杂化物的表面表现出两亲性，从而提高了吸附剂与水相样品基质的相容性。该策略在实际药物样品的分析中被证明是稳健的，具有良好的线性、高回收率和令人满意的可重复性。这项工作证实，所提出的工具可能是增强中药（TCM）中 AAs 提取选择性的有前途的候选物。
