表面印迹磁性纳米微球结合液相微萃取捕获水环境中的手性药物

The chiral non-steroidal anti-inflammatory drug has been used widely in clinic. The transformation of the corresponding isomer might happen with the help of biological purification system without absorption and utlization by human beings, which were discharged into the enviroment. However, different enantiomers may show different biological toxicity, therefore it was suggested that single enantiomers of chiral drugs should be considered as separate contaminants due to their differing ecotoxicity within the aquatic enviroment. In order to efficiently, greenly and specifically enrichment the trace chiral drugs in the water enviroment, with the combination of surface molecular imprinting, magnetic nano-technology and dispersive liquid-liquid microextraction, so as to develop a new green extraction technology combining surface molecular imprinting magnetic nano-microsphere as the solid phase extraction and dispersive liquid-liquid microextraction, which has been applied to the pretreatment of sewage and aquatic organism samples. To solve the problem of leaking templates, the 2-phenyl propionic acid and its analogueswere defined as the template molecule for the preparation of molecularly imprinted polymer, to investigate the recognition mechanism and regularity of magnetic molecularly imprinted nano-micropheres by ways of dynamic adsorption experiments, statical equilibrium adsorption experiments, selective test of template and its analogues. So as to simultaneously determine several chiral drugs combined with dispersive liquid-liquid microextraction. The present investigation was aimed to assess the degradation rate, process and stereoselectivity of chiral non-steroidal anti-inflammatory drugs in the water enviroment.

手性非甾体抗炎药临床使用广泛，未经吸收、利用的手性药物进入水环境前经过生物净化系统后可能会发生对映异构体的转化，而不同对映体的生物毒性可能差别很大，因而单一对映体应该作为单独的污染物进行生态毒性评估。为了高效、绿色、专属性地富集水环境中的痕量手性药物，将表面分子印迹、磁性纳米技术、分散液液微萃取有机结合，构建基于表面分子印迹磁性纳米微球的新型固相萃取与分散液液微萃取耦合的绿色提取技术，并将其用于污水和水生生物体内样品的前处理。为解决模版泄露问题，以2-苯基丙酸及其类似物为假模板分子制备分子印迹聚合物，通过动力学吸附实验、静态平衡吸附实验、模板及其类似物的选择性试验，考察磁性分子印迹纳米微球的识别机理和规律，结合高富集效率的分散液液微萃取技术从而实现对多种手性非甾体抗炎药的同时富集。旨在评估手性非甾体抗炎药在水环境中的降解速率、过程和立体选择性，从而为手性药物的生态毒性和污染物溯源提供依据。

分子印迹聚合材料是一种多孔材料，具有良好的选择性、高吸附容量、优异的机械稳定性和化学稳定性等优点，可以从复杂的样品基质中选择性的吸附目标分子或其结构类似物，可作为食品、生物和环境样品分析中理想的固相吸附剂。非甾体类抗炎药是一类减轻疼痛，发热和炎症的止痛药；主要通过人体排泄物释放到水生环境中。尽管其在环境中的浓度很低，但在环境中的持续释放所导致的长时间暴露会对非目标生物产生不利影响。开发灵敏可靠的分析方法来检测环境中的非甾体抗炎药，对于保护环境生态健康具有重要意义。.本课题采用多步种球溶胀法和多壁碳纳米管表面沉淀聚合法，合成了两种不同的非甾体抗炎药分子印迹聚合物MIPs1和MWNTs@MIPs，并对其合成条件进行优化。通过恒温吸附实验、动力学吸附实验和选择性试验，对合成分子印迹材料MIPs1和MWNTs的吸附性能进行考察。实验结果：① MIPs1 的Scatchard拟合分析表明，其对模版分子布洛芬存在两种结合位点，其中低吸附位点和高吸附位点的平衡解离常数Kd和最大表观吸附量Qmax分别为35.70 μmmol·L-1，294.12 μmmol·L-1和11.879 μmmol·g-1，22.029 μmmol·g-1；吸附动力学曲线表明，其在90 min达到吸附平衡。② MWNTs@MIPs对5种芳基丙酸类NSAIDs（洛索洛芬钠、酮洛芬、萘普生、氟比洛芬和布洛芬）均只有一种结合位点，平衡解离常数Kd和最大表观吸附量Qmax分别为250~2000.0 mg·L-1和86.65~990.2 mg·g-1，其吸附动力学结果表明，当t为5 min时，对5种芳基丙酸类NSAIDs均达到吸附平衡。实验结果表明，MIPs1和MWNTs@MIPs与其相对应的非分子印迹材料相比，对目标分子均具有较大的吸附能力和较高的选择特异性。.同时，将合成的分子印迹材料MIPs1和MWNTs@MIPs分别作为固相萃取和微固相萃取吸附剂，使用MISPE和μ-SPE-DLLME技术对不同水环境中（河水、湖水、自来水、灌溉水、污水）的9种非甾体抗炎药（布洛芬、水杨酸、对乙酰胺基酚、酮洛芬、吡罗昔康、吲哚美辛、洛索洛芬钠、萘普生和氟比洛芬）进行富集，并联用UPLC-MS/MS法对其准确定量测定。本研究所建立的两种方法，为实现不同水环境中痕量物质的定量分析，提供了依据。