【作者】 陈佳；

【导师】 肖玉秀；

【作者基本信息】 武汉大学 ， 药物分析学， 2019， 硕士

【摘要】 萃取技术的微型化和萃取溶剂的绿色化是绿色分析化学的发展趋势。超分子溶剂（supramolecular solvent,SUPRAS）和低共熔溶剂（deep eutectic solvent,DES）作为新一代绿色溶剂,在液相萃取领域均发展迅速。SUPRAS具有化学组成和结构的可控性、对生物大分子的限制进入特性以及非挥发性和不可燃性等特点,是一种灵活、高效、安全的萃取溶剂。DES具有易于制备、成本低廉、纯度高、挥发性低、环境友好等优越性质。但是,现有SUPRAS存在形成条件严苛、微量低密度萃取相难收集等问题,DES的发展仍存在诸如室温下为液态的疏水性DES较少、对非极性化合物的萃取能力低等问题。因此,研究形成条件温和的高密度超分子溶剂和凝固点低的疏水性DES对于液相微萃取技术的发展具有重要意义。本论文以具有多种优良特性的HFIP和环境友好的非离子表面活性剂为研究对象,制备了基于HFIP/非离子表面活性剂的SUPRAS和DES,研究了两种新型溶剂的理化性质,并分别构建了基于两种新型溶剂的液相微萃取方法（liquid-phase microextraction,LPME）。具体研究内容如下:（1）成功构建了HFIP/Brij-35/H₂O超分子溶剂体系,并将基于HFIP/Brij-35超分子溶剂的液相微萃取结合HPLC-DAD,用于环境水、药品和个人护理产品中六种对羟基苯甲酸酯的萃取和定量检测。系统研究了HFIP/Brij-35超分子溶剂体系的相行为、微观结构以及形成机理。结果表明,少量的HFIP（0.4%-1.7%,v/v）即可大幅降低Brij-35水溶液的浊点（>100 ^oC）,并在室温（甚至0 ^oC）和宽范围（0.5%-10%Brij-35,g/m L）条件下迅速诱导形成稳定、小体积（相率在0.013-0.111之间）、高密度的超分子溶剂。HFIP/Brij-35 SUPRAS由胶束聚集体（2-8μm）组成,可以与目标分析物产生强的氢键和疏水相互作用。此外,SUPRASs的体积和组成具有环境响应性,通过调控体系条件可以合成具有特定体积和组成的SUPRAS,为实际应用中萃取条件的优化提供了方向和依据。通过Plackett-Burman设计（PBD）和中心复合设计（central composite design,CCD）构建响应面模型获得了最佳萃取条件。在最优条件下,对羟基苯甲酸酯在2-400倍定量限范围内的定量线性关系良好（相关系数>0.9990）,检测限在0.042至0.167μg/L范围,富集因子达到26-193,分析物的回收率在92.9%-108.1%之间,日内和日间精密度（RSDs,n=3）分别小于6.8%和7.9%。将该方法分别用于分析实际样品中的对羟基苯甲酸酯,回收率在90.2%-112.4%之间,RSD均低于8.9%;除自来水样品外,其他样品均有检测到一种或多种对羟基苯甲酸酯。本方法是一种简单快速（萃取时间3.3 min）、环境友好（有机溶剂用量0.3 m L）、灵敏度高的样品预处理方法。（2）以HFIP为氢键供体、非离子表面活性剂（Brij-35、PONPE-7.5、Triton X-100、Triton X-114）为氢键受体,合成了疏水性DESs;将其作为萃取剂,构建了基于疏水性DES的涡旋辅助液相微萃取方法;并将该萃取方法与HPLC联用,应用于检测番茄辣椒酱样品中的5种苏丹违禁色素。理化性质研究结果表明,该类DESs凝固点均低于-10 ^oC,可在室温下稳定存在,且粘度和极性可调、密度比水大。微观结构分析表明,萃取后形成的DES富集相以DES/水/DES类似复合乳剂形态的聚集体结构存在,可与分析物之间产生更强的氢键和疏水相互作用力。通过单因素优化、显著性因素筛选实验以及响应曲面设计,得到最优萃取条件。采用内标标准曲线法定量,5种苏丹色素在0.04-2μg/g范围内定量线性关系良好（R>0.9997）,检测限在0.0045-0.0118μg/g之间,三种加标浓度样品方法回收率在91.6%-104.5%之间,日内和日间精密度（RSDs）均小于8.0%。将该方法应用于5种番茄酱样品的检测,回收率在87.5%-110.1%之间,RSD均小于7.1%,其中一个样品中检测到苏丹Ⅰ。本方法萃取时间短（4 min）,消耗有机溶剂少（0.1m L）,是一种简便、环保、高效、准确、可靠的样品预处理方法。更多还原

【Abstract】 The miniaturization of extraction technology and the greening of extraction solvents are the development trend of green analytical chemistry.As a new generation of green solvents,supramolecular solvent（SUPRAS）and deep eutectic solvent（DES）have been rapidly developed in the liquid-liquid extraction（LLE）field.SUPRAS is a flexible,efficient and safe extraction solvent with its chemical composition and structure controllability,restricted entry characteristics to biomacromolecules,and non-volatile and non-flammable properties.DES is easy to prepare,low in cost,high in purity,and has excellent properties such as low volatility,good biocompatibility and environmental friendliness.However,the existing SUPRASs have the problems of strict formation conditions and difficulty in collecting the small amount of low-density extraction phase,and the development of existing DES still has the following shortcomings:most of DESs are miscible with water and are not in liquid state under room temperature;the extraction efficiency for non-polar compounds is poor.Therefore,it is of great significance to study SUPRAS with high density and mild extraction conditions and hydrophobic DESs with a low freezing point for the development of new green solvents in the field of LLE.In this paper,HFIP（with several superior properties）and nonionic surfactants（environmentally friendly）were used as the main research objects.The green solvents SUPRAS and DES based on HFIP/non-ionic surfactant were prepared and the physicochemical properties of the solvents were characterized,and the LLMEs based on SUPRAS and DES were proposed,respectively.The specific research contents are as follows:（1）The HFIP/Brij-35/H₂O SUPRAS system was successfully developed,HFIP/Brij-35 SUPRAS-based LPME was coupled with HPLC-DAD for the extraction and quantitative detection of parabens in water samples,pharmaceuticals and personal care products.The phase behavior,microstructure and the formation mechanism of HFIP/Brij-35 SUPRAS were systematically studied.The results show that a little amount of HFIP（0.4%-1.7%,v/v）can drastically reduce the cloud point（>100 ^oC）of Brij-35 aqueous solution and rapidly induce the formation of a stable,low-volume（the phase ratio was between 0.013-0.111）,high-density SUPRAS over a wide range of conditions（0.5-10%Brij-35,g/m L）at room temperature（even 0 ^oC）.The HFIP/Brij-35 SUPRAS consists of micelle aggregates（2-8μm）and can generate strong hydrogen-bonding and hydrophobic interactions with target analytes.In addition,the volume and composition of HFIP/Brij-35 SUPRASs are environmentally responsive,and the SUPRAS with specific volume and composition could be synthesized over a wide liquid-liquid two-phase region,which undoubtedly beneficial for the optimization of extraction conditions in real applications.The optimal extraction conditions were obtained by constructing the response surface model by Plackett-Burman design（PBD）and central composite design（CCD）.Under the optimal conditions,the linear correlation coefficient was good in the range of 2-400 times LOQs,（R>0.9990）,the LODs were ranged from 0.042 to 0.167μg/L,and the enrichment factors were 26-193.The recoveries of the analytes ranged from 92.9%to 108.1%,and the intra-day and inter-day precision（RSDs,n=3）were less than 6.8%and 7.9%,respectively.The recoveries for the spiked real samples were in the range of 90.2%–112.4%with relative standard deviation less than 8.9%.Except for tap water,one or several paraben（s）were detected in all the other real samples.The method was a simple and fast（extraction time is 3 min）,environmental friendly（organic solvent consumption is 0.3 m L）sample preparation method with high sensitivity.（2）New hydrophobic DESs were synthesized using HFIP as a hydrogen bond donor and nonionic surfactants（Brij-35,PONPE-7.5,Triton X-100,Triton X-114）as hydrogen bond acceptors,vortex-assisted DES based LPME coupled with HPLC was introduced to determine five Sudan dyes in tomato chili sauces.The physical and chemical properties of DESs were studied and the results showed that the freezing point of these DESs was lower than-10 ^oC,which can be stably existed at room temperature,the viscosities and polarities of DESs were adjustable,and the densities of DESs were higher than water.Through observation of the microstructure of DES-rich phase,a DES/water/DES like composite emulsion structure was in sight,which strengthen the hydrophobic and hydrogen bonding interactions between DESs and analytes.One-variable-at-a-time（OVAT）,significant factor screening experiments and response surface methodology（RSM）were used to obtain the best extraction condition.The internal standard curve was plotted for method evaluation and the quantitative detection of Sudan in five real samples.For the five Sudan dyes,under 0.04-2μg/g concentrations,the regression coefficients were higher than 0.999,the LODs were between 0.0045-0.0118μg/g,and the recoveries of the three spiked samples were in the range of 91.6%-104.5%,and the intra-day and inter-day precision（RSDs）were less than 8.0%.The method was applied to the detection of five kinds of tomato samples,the recovery was between 87.5%-110.1%,and the RSD was less than 7.1%,and Sudan I was detected in one sample.The proposed method requires a short extraction time and consumes less organic solvent,which is a simple,environmentally friendly and efficient sample preparation method.更多还原