液相微萃取法测定血清中药物浓度
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摘要
中空纤维膜液相微萃取是一项新的样品前处理技术,该技术以具有一定大小孔径的中空纤维膜为萃取有机溶剂的载体,当利用中空纤维膜液相微萃取进行萃取实验时,因有机溶剂不直接与样品溶液相接触,从而避免了有机溶剂对样品的干扰。同时该技术集采样、萃取、浓缩于一体。因为药物在有机溶剂中有较大的溶解度,所以能够得到高灵敏度。实验中中空纤维膜只适用一次,避免了交叉污染;另外,中空纤维膜液相微萃取实验操作简单,试验者可以自行设计实验装置。
本文分为五个部分,扩展了中空纤维膜液相微萃取的应用,并且对实验装置进行了设计和研究。
首先,对液相微萃取的发展和应用做了较细致的总结,阐述了中空纤维膜液相微萃取常用的三种萃取模式(液液两相微萃取、液液液三相微萃取、载体转运萃取)的原理和应用范围。本文还对实验中的主要影响因素进行了归纳,分析了优化实验条件的方法途径。
本文提出一种新的测定血清中药物的方法,即,结合药物在水相和有机相之间的平衡常数与其血清蛋白结合率来测定血清中药物浓度,该方法不用加入有机溶剂沉淀蛋白,因此省去了沉淀、离心、挥发有机溶剂等操作步骤,实验相对误差小,完全可以作为一种新的血清中药物浓度测定方法;其次,结合有机溶剂沉淀蛋白使药物游离对血清中低浓度药物进行定量,以达到提高灵敏度的目的。
作为定量的前提还准确测定了吲哚美辛和醋酸地塞米松两种药物的蛋白结合率,并对实验影响因素进行了考察。利用中空纤维膜液相微萃取来测定药物的蛋白结合了率,因有机溶剂不直接与生物样品接触,对蛋白活性几乎没有影响,本方法与经典平衡透析法相比,具有所需实验时间短等优点。与超滤法相比,有机膜面积非常小,使用样品量小,克服了药物在膜上的吸附问题。
本文还对实验装置进行了探索研究,根据膜的性质以及与有机溶剂的兼容性等,选取了聚丙烯、透析膜、聚四氟乙烯三种材料的膜进行实验,从静态萃取和动态萃取两个方面对聚丙烯膜进行考察,而透析膜和聚四氟乙烯膜则是选择水溶性的对甲苯磺酸进行动力学考察。
Hollow fiber membrane micro extraction is a new technique which is used to be a sample retreatment method In this technique, a section of hollow fiber membrane is used as the carrier of organic solvent In the membrane wall, many holes are well-distributed These holes have fixed size The existence of membrane can prevent the organic solvent touch with sample solution directly So this technique can avoid the extraction solvent effect the sample solution. At the same time, it can get extraction, cleaning and concentration together The membrane can prevent the macromolecule into extraction solvent Because fat-soluble drug has good dissolubility in organic solvent, analyte can be enriched in extraction organic solvent The hollow fiber is disposable, and cross-contamination can be avoided In addition, the hollow fiber membrane micro extraction is easy to operate
In this thesis, new applications of liquid micro extraction are studied deeply, which is divided into six chapters
First, the review summarizes the development and application of the liquid phase micro extraction, introduces the devices which reported in literature and these advantages and disadvantages, describe three extraction models which are used generally Such as: liquid-liquid two phase extraction, liquid-liquid-liquid three phases extraction, carrier transport This thesis also summarizes the main factor which affect the experiment result, analyze the method which optimization condition of experiment
In the experiment part, we set up a new method which is used to detect the concentration of sample in serum In this method, the protein is not need to be moved, the procedure is simpler than others It without precipitation, centrifugalization and volatilize However, we remove the protein before detecting, so as to raise the sensitivity
We detect the protein binding ratio of two drugs precisely, at the same time we consider the main effect factor Detect the protein binding ratio by hollow fiber membrane micro extraction , the organic solvent does not touch with protein, so it’s activity is not be affected Compared with equilibrium dialysis it need very short time Compared with ultrafiltration sample consume is little
In the last chapter, we design devices and do many studies about these devices We chose polypropylene membrane, dialysis-membrane and polytetrafluoroethylene membrane as materials
本文分为五个部分,扩展了中空纤维膜液相微萃取的应用,并且对实验装置进行了设计和研究。
首先,对液相微萃取的发展和应用做了较细致的总结,阐述了中空纤维膜液相微萃取常用的三种萃取模式(液液两相微萃取、液液液三相微萃取、载体转运萃取)的原理和应用范围。本文还对实验中的主要影响因素进行了归纳,分析了优化实验条件的方法途径。
本文提出一种新的测定血清中药物的方法,即,结合药物在水相和有机相之间的平衡常数与其血清蛋白结合率来测定血清中药物浓度,该方法不用加入有机溶剂沉淀蛋白,因此省去了沉淀、离心、挥发有机溶剂等操作步骤,实验相对误差小,完全可以作为一种新的血清中药物浓度测定方法;其次,结合有机溶剂沉淀蛋白使药物游离对血清中低浓度药物进行定量,以达到提高灵敏度的目的。
作为定量的前提还准确测定了吲哚美辛和醋酸地塞米松两种药物的蛋白结合率,并对实验影响因素进行了考察。利用中空纤维膜液相微萃取来测定药物的蛋白结合了率,因有机溶剂不直接与生物样品接触,对蛋白活性几乎没有影响,本方法与经典平衡透析法相比,具有所需实验时间短等优点。与超滤法相比,有机膜面积非常小,使用样品量小,克服了药物在膜上的吸附问题。
本文还对实验装置进行了探索研究,根据膜的性质以及与有机溶剂的兼容性等,选取了聚丙烯、透析膜、聚四氟乙烯三种材料的膜进行实验,从静态萃取和动态萃取两个方面对聚丙烯膜进行考察,而透析膜和聚四氟乙烯膜则是选择水溶性的对甲苯磺酸进行动力学考察。
Hollow fiber membrane micro extraction is a new technique which is used to be a sample retreatment method In this technique, a section of hollow fiber membrane is used as the carrier of organic solvent In the membrane wall, many holes are well-distributed These holes have fixed size The existence of membrane can prevent the organic solvent touch with sample solution directly So this technique can avoid the extraction solvent effect the sample solution. At the same time, it can get extraction, cleaning and concentration together The membrane can prevent the macromolecule into extraction solvent Because fat-soluble drug has good dissolubility in organic solvent, analyte can be enriched in extraction organic solvent The hollow fiber is disposable, and cross-contamination can be avoided In addition, the hollow fiber membrane micro extraction is easy to operate
In this thesis, new applications of liquid micro extraction are studied deeply, which is divided into six chapters
First, the review summarizes the development and application of the liquid phase micro extraction, introduces the devices which reported in literature and these advantages and disadvantages, describe three extraction models which are used generally Such as: liquid-liquid two phase extraction, liquid-liquid-liquid three phases extraction, carrier transport This thesis also summarizes the main factor which affect the experiment result, analyze the method which optimization condition of experiment
In the experiment part, we set up a new method which is used to detect the concentration of sample in serum In this method, the protein is not need to be moved, the procedure is simpler than others It without precipitation, centrifugalization and volatilize However, we remove the protein before detecting, so as to raise the sensitivity
We detect the protein binding ratio of two drugs precisely, at the same time we consider the main effect factor Detect the protein binding ratio by hollow fiber membrane micro extraction , the organic solvent does not touch with protein, so it’s activity is not be affected Compared with equilibrium dialysis it need very short time Compared with ultrafiltration sample consume is little
In the last chapter, we design devices and do many studies about these devices We chose polypropylene membrane, dialysis-membrane and polytetrafluoroethylene membrane as materials
引文
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[2] Jeannot M A,Cantwell F F,Solvent micro extraction into a single drop,Anal.Chem.,1996, 68: 2236～2240
[3] Pedersen-Bjgraard S,Rasmussen K E,Liquid-liquid-liquid micro extraction for sample preparation of biological fluid prior to capillary electrophoresis, Anal Chem., 1999, 71: 2660～2656
[4] Jeannot M A,Cantwell F F, Mass transfer characteristics of solvent extraction into a single drop at the tip of a syringe needle, Anal Chem., 1997, 69: 235
[5]杨新磊,罗明标等,液相微萃取技术在生物样品检测中的应用,药物分析学杂志,2007,27 (12): 1998～2002
[6] Zhu L, Lee H K, Liquid-liquid-liquid micro extraction of nitrophenols with a hollow fiber membrane prior to capillary liquid chromatography, J Chromatography A, 2001, 924(1-2): 407
[7]罗明标,刘维等,多孔中空纤维液相微萃取技术的研究进展,分析化学,2007, 7: 1071～1077
[8] Wu H F, Jyh H Y, Chen C C, Combining drop-to-drop solvent micro extraction with Gas chromatography/Mass spectrometry using electronic ionization and self-Ion/Molecule reaction method to determine methoxyacetophenone isomers in one drop of water, Anal Chem., 2006, 78: 1707～1712
[9] Muller S, Moder M, Schrader S et al, Semi-automated hollow fiber membrane micro extraction, a novel enrichmemt technique for the determination of biologically active compounds in water samples, J Chromatgr A, 2003, 985: 99～106
[10] Li N, Deng C H, Yao N, et al, Determination of acetone, hesanal and heptanal in blood samples by derivatization with pentafluorobenzyl hydroxylamine followed by headspace single-drop micro extraction and gas chromatography-mass spectrometry, Anal Chim, Acta, 2005, 540: 317～323
[11] Myung S W, Yoon S H, Kim M Analysis of benzene ethylamine derivatives in urine using the programmable dynamic liquid-phase micro extraction (LPME) device, Analyst, 2003, 128: 1443
[12] Lambropoulou D A, Psillakis E, Albainis T A, et al Single– drop micro extraction for the analysis of organophosphorous in secticides in water, Anal Chim Acte, 2004, 516: 205～211
[13] Assadi A F, Hosseini Y, Milani S M R, et al, Determination of organophorous pesticides in water samples by single drop micro extraction and gas chromatography-flame photometric detector, J Chromatogr A, 2006, 1101: 307～312
[14] Dubey D K, Pardasani D, Gupta A K et al, Hollow fiber–mediated liquid– phase micro extraction of chemical warfare agents from water, J Chromatogr A, 2006, 1107: 29～35
[15] Chen C C, Melwanki M B, Huang D, Liquid– liquid-liquid micro extraction with automated movement of acceptor and the donor phase for the extraction of phenoxyacetic acids prior to liquid chromatography detection, J Chromatogr A, 2006, 1104: 33～39
[16] Wu J M, Ee K H, Lee H K Automated dynamic liquid– liquid–liquid micro extraction follwed by high– performance liquid of phenoxy acid herbicides in environmental waters, J Chromatogr A, 2005, 1082: 121～127
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