手性喹诺酮类抗生素在水-沉积物体系中的立体选择性迁移转化行为研究

Antibiotics pollution in the aquatic environment is one of research topic currently. Quinolones is widely applied in aquaculture industry and broadly remain in water body for its easy to deposit in sediment. Recent research is limit to detect the concentration of the residue in water environment instead of doing depth and systematic study on migration and transformation behaviors. Besides, that the chiral characteristics of Quinolones and their metabolites as well as the different toxicity of enantiomers are neglected is the reason that we cannot accurately evaluate the dietary and environment risks. This project selects ofloxacin and flumequine as the research objects and will develop chiral analytical methods of these drugs and their metabolites enantiomers in water and sediment. On the basis, the affecting factors of stereoselective adsorption and transformation rules of the enantiomers of ofloxacin and flumequine in sediment will be investigated. Simultaneously, the enantioselective behaviors of movement, distribution, transformation and degradation rules of parent compounds and its chiral metabolites in the water-sediment system will be investigated through the laboratory culture and pond trials studies. The residue results will be compared with the mathematical models prediction. This study will provide important theoretical significance and actual value for the chiral quinolones research on environmental ecology risk assessment and thus provide test basis for the scientific use of this drugs.

抗生素对水体环境污染问题是目前研究热点之一，喹诺酮类抗生素广泛应用于水产养殖业，此类药物进入水体后易在沉积物中富集，长期残留在养殖水体中。部分喹诺酮类药物及其代谢物具有手性特征，现有研究忽略其对映体的差异，并且多限于对残留水平的检测，缺乏其在水体环境中迁移转化等行为的系统研究，因此不能准确评价环境风险。本项目以水产养殖常用的氧氟沙星和氟甲喹为研究对象，建立水和沉积物中氧氟沙星、氟甲喹及手性代谢物的对映体分离分析方法，以此为基础考察氧氟沙星和氟甲喹对映体在沉积物中的立体选择性吸附和转化规律及影响因素。同时通过实验室模拟水环境和小型池塘试验，在对映体水平上研究母药及代谢物在水-沉积物体系中的富集、分布、转化、降解等环境行为以及产生选择性的机理。最后尝试建模分析药物结构与降解行为间的关系。本研究为两种药物科学合理使用提供依据，对更准确评价此类药物的生态环境风险具有重要的理论意义与实际价值。

喹诺酮类抗生素广泛应用于水产养殖业，此类药物进入水体后易在沉积物中富集，长期残留在环境中。部分喹诺酮类药物及其代谢物具有手性特征，现有研究忽略其对映体的差异，因此不能准确评价其环境风险。本项目分别采用手性Lux Cellulose-2，Lux Cellulose-4和CHIRALCEL OD-H拆分柱，拆分制备氟甲喹，七羟基氟甲喹以及氧氟沙星的对映异构体。并建立氟甲喹和氧氟沙星对映体在水-沉积物体系中的痕量分析方法。. 吸附试验结果表明，氟甲喹两个对映体在沉积物中均具有明显的选择性吸附差异，单体吸附量大于外消旋吸附量。吸附选择性与沉积物性质有关，氟甲喹在偏碱性沉积物中发生异构体选择性吸附差异。. 降解试验结果表明，氟甲喹在沉积物中的消解行为基本符合一级动力学方程，微生物在氟甲喹降解过程中起着极其重要的作用。氟甲喹对映异构体在沉积物中未发生构型反转，但在沉积物中的降解速率存在异构体选择性差异，其右旋降解速率均大于左旋，研究结果表明选择性降解是由微生物降解产生的，降解速率和选择性强弱均受沉积物微生物影响。