臺灣博碩士論文加值系統

RS-Carvedilol藥物作為治療心力衰竭、高血壓，RS-Terbutaline與RS-Metaproterenol藥物作為治療支氣管的擴張劑。本研究分為兩部分，第一部分為快速分離RS-Carved、RS-Terbut、RS-Metapro 三種藥物，藉由添加掌性選擇劑 DM-β-CD及高分子溶液poly (diallyldimethylam monium chloride) (PDDAC)於甲酸緩衝溶液中；此部分最佳分離條件為pH 2.5、100 mM的甲酸緩衝溶液中含有5 mM DM-β-CD及0.9 % PDDAC，成功地將RS-Carved、RS-Terbut、RS-Metapro 三種藥物及內標物(Losartan)於10分鐘內完成分離。第二部分使用分散式液液微萃取法(DLLME)為樣品前處理方法，在最佳條件下，將30 μL CH2Cl2 和200 μL ACN快速注入1mL的樣品溶液中，在極短的萃取時間內即可獲得121-124倍的高濃縮倍率，其線性範圍為0.09 -10 μΜ( r > 0.9956)。LOD範圍為0.014-0.017 μM，而RSD皆低於5.0 %。真實樣品方面，尿液樣品的相對回收率為74-123 %，且RSD皆低於6.8 %；血清樣品的相對回收率為70-132 %，且RSD皆低於8.9 %。

This study was divided into two parts . First, rapid enantioseparation of three basic drugs (RS-Carvedilol, RS-Terbutaline, and RS-Metaproterenol ) was performed , with dimethyl-β-cyclodextrin (DM-β-CD) as the chiral selector and poly(diallyldimethylammonium chloride) (PDDAC) in the background electrolyte as buffer additive. Under optimized conditions, the separation system－which comprised 5mM DM-β-CD and 0.9 % PDDAC at pH 2.5 , with a capillary length of 35 cm, enabled three pairs of RS-Carvedilol, RS-Terbutaline, and RS-Metaproterenol and internal standard (losartan potassium) to be successfully separated in 10 min. Second, dispersive liquid－liquid microextraction was used in capillary electrophoresis. Under optimum conditions,the use of 1.00 mL of sample solution, 30 μL of dichloromethane as the extraction solvent, and 200 μL of acetonitrile as the dispersive solvent and, yielded a high enrichment factor in the range of 121－124 at an extraction time of less than 3 min. Moreover, a strong linearity was obtained from 0.09－to 10 μM (r >0.9956). In real samples, the recoveries of RS-Carvedilol from urine and serum samples were in the ranges of 74 %－123 % and 70 %－127 % , respectively.

目錄
摘要 I
目錄 III
壹、緒論 1
一、β -腎上腺素受體抑制劑、刺激劑簡介 1
1.1分析物簡介 2
二、藥物分析方法 5
三、環糊精簡介 9
四、聚二甲基二烯丙基氯化銨(PDDAC) 12
五、毛細管電泳簡介 13
5.1 毛細管區帶電泳(CZE) 15
5.2 微胞電動層析法(MEKC) 16
六、萃取方法之簡介 18
6.1 液-液萃取法(Liquid-liquid extraction, LLE) 18
6.2 固相萃取法(Solid-phase extraction, SPE) 19
6.3固相微萃取法(Solid-phase microextraction, SPME) 20
6.4 液相微萃取法(Liquid-phase microextraction, LPME) 21
6.5 分散式液液微萃取法(Dispersive Liquid-Liquid Microextraction, DLLME) 22
七、研究動機與目的 25
貳、實驗 26
一、儀器設備 26
二、藥品 27
三、實驗方法 30
3.1 CE-UV偵測系統 30
3.2儲存溶液的配製 31
3.3緩衝溶液的配製 32
3.4 毛細管電泳處理與進樣方式 32
3.5分散式液液微萃取步驟 32
3.6 尿液樣品直接分析 33
3.7 尿液樣品經分散式液液微萃取後分析 33
3.8 血清樣品直接分析 34
3.9 血清樣品經分散式液液微萃取後分析 34
參、結果與討論 35
一、毛細管電泳分離條件探討 36
1.1 pH值對於分離的影響 37
1.2 環糊精種類對於分離的影響 40
1.3 緩衝溶液種類對於分離的影響 43
1.4 環糊精濃度對於分離的影響 46
1.5 添加HDB、PDDAC、CTAB、TTAB的分離效果比較 49
1.6 PDDAC含量對於分離的影響 52
1.7 離子強度對於分離的影響 55
1.8 毛細管長度對分離的影響 58
1.9 最佳分離條件 60
二、分散式液液微萃取法條件優化 61
2.1 萃取劑的選擇 62
2.2 萃取劑體積的影響 65
2.3 分散劑的選擇 67
2.4 分散劑體積的影響 69
2.5 溶液pH值的影響 71
2.6萃取時間的影響 73
2.7 鹽類添加量的影響 75
2.8 分散式液液微萃取的最佳條件 77
三、方法確效 79
3.1 標準樣品直接分析 79
3.2 標準樣品經分散式液液微萃取後分析 80
四、生物樣品的應用 83
4.1 尿液樣品的分析 83
4.2 尿液樣品的定量、靈敏度、精密度與準確度 85
4.3血清樣品的分析 89
4.4血清樣品的定量、靈敏度、精密度與準確度 91
肆、結論 95
參考文獻 96

圖目錄
圖1、環糊精的外觀 10
圖2、環糊精結構示意圖 10
圖3、PDDAC結構 12
圖4、CE平面流型與HPLC之拋物線流型 14
圖5、毛細管區帶電泳(CZE)分離示意圖 15
圖6、微胞電動層析(MEKC)分離示意圖 17
圖7、固相萃取法(SPE)示意圖 20
圖8、分散式液液微萃取(DLLME)示意圖 24
圖9、毛細管電泳儀器示意圖 30
圖10、緩衝溶液pH值變化 38
圖11、緩衝溶液添加不同種類環糊精探討 41
圖12、緩衝溶液種類探討 44
圖13、緩衝溶液添加不同濃度之DM-β-CD的探討 47
圖14、緩衝溶液添加HDB、PDDAC、CTAB、TTAB分離效果探討 50
圖15、緩衝溶液添加PDDAC含量變化 53
圖16、緩衝溶液離子強度變化 56
圖17、毛細管總長度變化 59
圖18、最佳條件分離圖 60
圖19、萃取劑種類的影響 64
圖20、萃取劑體積的影響 66
圖21、分散劑種類的影響 68
圖22、分散劑體積的影響 70
圖23、溶液pH值的影響 72
圖24、萃取時間的影響 74
圖25、鹽類添加的影響 76
圖26、分散式液液微萃取最佳條件標準層析圖 78
圖27、尿液樣品和添加分析物經DLLME分析 84
圖28、尿液萃取最低濃度 87
圖29、血清樣品和添加分析物經DLLME分析 90
圖30、血清萃取最低濃度 94

表目錄
表 1、分析物Carved、Terbut、Metapro及內標Losartan的化學結構及其物性 4
表2、使用不同偵測儀器與樣品前處理應用於Carved、Terbut、Metapro藥物的分析 7
表2、使用不同偵測儀器與樣品前處理應用於Carved、Terbut、Metapro藥物的分析(接續前頁) 8
表3、α、β、γ環糊精的性質 11
表4、三種分析物在不同pH值的理論板數 39
表5、三種分析物在不同環糊精的解析度 42
表6、三種分析物在不同緩衝溶液的解析度 45
表7、三種分析物在不同濃度之環糊精的解析度 48
表8、將HDB、PDDAC、CTAB、TTAB添加在緩衝溶液中三種分析物的解析度 51
表9、三種分析物在不同濃度PDDAC的解析度 54
表10、三種分析物在不同離子強度的緩衝溶液環境下的解析度 57
表11、萃取劑之性質 63
表12、分散劑的極性 67
表13、分散式液液微萃取最佳條件 77
表14、標準樣品直接分析 81
表15、標準樣品經分散式液液微萃取後分析 82
表16、尿液樣品結合分散式液液微萃取 86
表17、尿液樣品經添加後之準確度與精密度 88
表18、血清樣品結合分散式液液微萃取 92
表19、血清樣品經添加後之準確度與精密度 93

1.Freemantle, N.; Cleland, J.; Young, P.; Mason, J.; Harrison, J., β Blockade after myocardial infarction: systematic review and meta regression analysis. Bmj 1999, 318 (7200), 1730-1737.
2.Lee, H.-B.; Sarafin, K.; Peart, T. E., Determination of β-blockers and β 2-agonists in sewage by solid-phase extraction and liquid chromatography–tandem mass spectrometry. Journal of Chromatography A 2007, 1148 (2), 158-167.
3.Frishman, W. H.; Cheng-Lai, A.; Nawarskas, J., Current cardiovascular drugs. Springer Science & Business Media: 2005.
4.Arcangelo, V. P.; Peterson, A. M., Pharmacotherapeutics for advanced practice: a practical approach. Lippincott Williams & Wilkins: 2006; Vol. 536.
5.Quirino, J. P.; Terabe, S., Sample stacking of cationic and anionic analytes in capillary electrophoresis. Journal of Chromatography A 2000, 902 (1), 119-135.
6.Clément, K.; Vaisse, C.; Manning, B. S. J.; Basdevant, A.; Guy-Grand, B.; Ruiz, J.; Silver, K. D.; Shuldiner, A. R.; Froguel, P.; Strosberg, A. D., Genetic variation in the β3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. New England Journal of Medicine 1995, 333 (6), 352-354.
7.Kubon, C.; Mistry, N. B.; Grundvold, I.; Halvorsen, S.; Kjeldsen, S. E.; Westheim, A. S., The role of beta-blockers in the treatment of chronic heart failure. Trends in Pharmacological Sciences 2011, 32 (4), 206-212.
8.Van der Vring, J.; Daniëls, M.; Holwerda, N.; Withagen, P.; Schelling, A.; Cleophas, T.; Hendriks, M., Combination of calcium channel blockers and beta blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. Angiology 1999, 50 (6), 447-454.
9.Stapleton, M. P., Sir James Black and propranolol. The role of the basic sciences in the history of cardiovascular pharmacology. Texas Heart Institute Journal 1997, 24 (4), 336.
10.Shao, B.; Jia, X.; Zhang, J.; Meng, J.; Wu, Y.; Duan, H.; Tu, X., Multi-residual analysis of 16 β-agonists in pig liver, kidney and muscle by ultra performance liquid chromatography tandem mass spectrometry. Food Chemistry 2009, 114 (3), 1115-1121.
11.Soltani, S.; Ramezani, A. M.; Soltani, N.; Jouyban, A., Analysis of losartan and carvedilol in urine and plasma samples using a dispersive liquid–liquid microextraction isocratic HPLC–UV method. Bioanalysis 2012, 4 (23), 2805-2821.
12.Yamini, Y.; Reimann, C. T.; Vatanara, A.; Jönsson, J. Å., Extraction and preconcentration of salbutamol and terbutaline from aqueous samples using hollow fiber supported liquid membrane containing anionic carrier. Journal of Chromatography A 2006, 1124 (1), 57-67.
13.Guttman, A., Novel separation scheme for capillary electrophoresis of enantiomers. Electrophoresis 1995, 16 (1), 1900-1905.
14.Quintero, B.; Lopez, J.; Thomas, J., Determination of dissociation constants of 5‐[1‐hydroxy‐2‐[(1‐methylethyl) amino] ethyl]‐1‐3‐benzenediol. Journal of pharmaceutical sciences 1985, 74 (1), 72-75.
15.Hernandez Gaina A, Ph.D. Thesis, University of Granada, 1982.
16.Peccinini, R. G.; Ximenes, V. F.; Cesarino, E. J.; Lanchote, V. L., Stereoselective analysis of carvedilol in human plasma and urine using HPLC after chiral derivatization. Biopharmaceutics & Drug Disposition 2008, 29 (5), 280-288.
17.Dunn, C. J.; Lea, A. P.; Wagstaff, A. J., Carvedilol. Drugs 1997, 54 (1), 161-185.
18.Fleisher, D.; Sweet, B. V.; Parekh, A.; Boullata, J. I., Drug absorption with food. In Handbook of Drug-Nutrient Interactions, Springer: 2009; pp 209-241.
19.Campoli, R.; Sorkin, E., Carvedilol: A review of its pharmacodynamic and pharmacokinetic properties and therapeuetic efficiacy. Drugs 1993, 45, 232-258.
20.Morgan, T., Clinical pharmacokinetics and pharmacodynamics of carvedilol. Clinical Pharmacokinetics 1994, 26 (5), 335-346.
21.Jouyban, A.; Sorouraddin, M. H.; Farajzadeh, M. A.; Somi, M. H.; Fazeli-Bakhtiyari, R., Determination of five antiarrhythmic drugs in human plasma by dispersive liquid–liquid microextraction and high-performance liquid chromatography. Talanta 2015, 134, 681-689.
22.GlaxoSmithKline, Carvedilol Package Insert. 1995.
23.Ho, K. K.; Hun, S. S.; Ju, K. H.; Young, J. E.; Jong-Seong, K.; Woongchon, M.; Rok, Y. J., Determination of terbutaline enantiomers in human urine by capillary electrophoresis using hydroxypropyl-β-cyclodextrin as a chiral selector. Archives of Pharmacal Research 2003, 26 (2), 120.
24.Dollery, C.; Boobis, A.; Burley, D., Therapeutic Drugs-vol2. 1991.
25.Li, S.; Wang, J.; Zhao, S., Determination of terbutaline sulfate by capillary electrophoresis with chemiluminescence detection. Journal of Chromatography B 2009, 877 (3), 155-158.
26.Knox, C.; Law, V.; Jewison, T.; Liu, P.; Ly, S.; Frolkis, A.; Pon, A.; Banco, K.; Mak, C.; Neveu, V., DrugBank 3.0: a comprehensive resource for'omics' research on drugs: Nucleic Acids Res. Database issue) D1035-41 2011.
27.Wishart, D. S.; Knox, C.; Guo, A. C.; Cheng, D.; Shrivastava, S.; Tzur, D.; Gautam, B.; Hassanali, M., DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Research 2007, 36 (suppl_1), D901-D906.
28.Hatch, F.; McKellop, K.; Hansen, G.; MacGregor, T., Relative bioavailability of metaproterenol in humans utilizing a single dose, stable isotope approach. Journal of Pharmaceutical Sciences 1986, 75 (9), 886-890.
29.Jouyban, A.; Sorouraddin, M. H.; Farajzadeh, M. A.; Somi, M. H.; Fazeli-Bakhtiyari, R., Vortex-assisted liquid–liquid extraction combined with field-amplified sample injection and sweeping micellar electrokinetic chromatography for improved determination of β-blockers in human urine. Talanta 2016, 149, 298-309.
30.Xia, Y. Q.; Liu, D. Q.; Bakhtiar, R., Use of online‐dual‐column extraction in conjunction with chiral liquid chromatography tandem mass spectrometry for determination of terbutaline enantiomers in human plasma. Chirality 2002, 14 (9), 742-749.
31.Leferink, J.; Wagemaker-Engels, I.; Maes, R.; Lamont, H.; Pauwels, R.; Van der Straeten, M., Quantitative analysis of terbutaline in serum and urine at therapeutic levels using gas chromatography—mass spectrometry. Journal of Chromatography B: Biomedical Sciences and Applications 1977, 143 (3), 299-305.
32.Hamidi, S.; Soltani, S.; Jouyban, A., A dispersive liquid–liquid microextraction and chiral separation of carvedilol in human plasma using capillary electrophoresis. Bioanalysis 2015, 7 (9), 1107-1117.
33.Clohs, L.; McErlane, K. M., Development of a capillary electrophoresis assay for the determination of carvedilol enantiomers in serum using cyclodextrins. Journal of Pharmaceutical and Biomedical Analysis 2001, 24 (4), 545-554.
34.Zamani-Kalajahi, M.; Fazeli-Bakhtiyari, R.; Amiri, M.; Golmohammadi, A.; Afrasiabi, A.; Khoubnasabjafari, M.; Jouyban, A., Dispersive liquid–liquid microextraction based on solidification of floating organic droplet followed by spectrofluorimetry for determination of carvedilol in human plasma. Bioanalysis 2013, 5 (4), 437-448.
35.Hokama, N.; Hobara, N.; Kameya, H.; Ohshiro, S.; Sakanashi, M., Rapid and simple micro-determination of carvedilol in rat plasma by high-performance liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications 1999, 732 (1), 233-238.
36.Xu, L. X.; Hui, N.; Ma, L. Y.; Wang, H. Y., Study on fluorescence property of carvedilol and determination of carvedilol by fluorimetry. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2005, 61 (5), 855-859.
37.Gannu, R.; Yamsani, V. V.; Rao, Y. M., New RP‐HPLC Method with UV‐Detection for the Determination of Carvedilol in Human Serum. Journal of Liquid Chromatography & Related Technologies 2007, 30 (11), 1677-1685.
38.Kim, K. H.; Kim, H. J.; Kim, J.-H.; Shin, S. D., Determination of terbutaline enantiomers in human urine by coupled achiral–chiral high-performance liquid chromatography with fluorescence detection. Journal of Chromatography B: Biomedical Sciences and Applications 2001, 751 (1), 69-77.
39.Deñola, N. L.; Quiming, N. S.; Catabay, A. P.; Saito, Y.; Jinno, K., Optimization of capillary electrophoretic enantioseparation for basic drugs with native β‐CD as a chiral selector. Electrophoresis 2006, 27 (12), 2367-2375.
40.Herring, V. L.; Johnson, J. A., Simple method for determination of terbutaline plasma concentration by high-performance liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications 2000, 741 (2), 307-312.
41.Ahmadi, F.; Karamian, E., Computational aided-molecular imprinted polymer design for solid phase extraction of metaproterenol from plasma and determination by voltammetry using modified carbon nanotube electrode. Iranian Journal of Pharmaceutical Research 2014, 13 (2), 417.
42.Cooke, W.; Moore, L. In QUANTIFICATION OF METAPROTERENOL (MET) IN PLASMA BY HPLC/ECD USING TERBUTALINE (TER) AS AN INTERNAL STANDARD, CLINICAL CHEMISTRY 1985, 942-942.
43.Fanali, S., Enantioselective determination by capillary electrophoresis with cyclodextrins as chiral selectors. Journal of Chromatography A 2000, 875 (1), 89-122.
44.Juvancz, Z.; Kendrovics, R. B.; Iványi, R.; Szente, L., The role of cyclodextrins in chiral capillary electrophoresis. Electrophoresis 2008, 29 (8), 1701-1712.
45.Luong, J. H.; Nguyen, A., Achiral selectivity in cyclodextrin-modified capillary electrophoresis. Journal of Chromatography A 1997, 792 (1), 431-444.
46.Fanali, S., Controlling enantioselectivity in chiral capillary electrophoresis with inclusion–complexation. Journal of Chromatography A 1997, 792 (1), 227-267.
47.Tseng, W.-L.; Chen, S.-M.; Hsu, C.-Y.; Hsieh, M.-M., On-line concentration and separation of indolamines, catecholamines, and metanephrines in capillary electrophoresis using high concentration of poly (diallyldimethylammonium chloride). Analytica Chimica Acta 2008, 613 (1), 108-115.
48.Yu, C. J.; Tseng, W. L., Online concentration and separation of basic proteins using a cationic polyelectrolyte in the presence of reversed electroosmotic flow. Electrophoresis 2006, 27 (18), 3569-3577.
49.Lauer, H. H.; McManigill, D., Capillary zone electrophoresis of proteins in untreated fused silica tubing. Analytical Chemistry 1986, 58 (1), 166-170.
50.McCormick, R. M., Capillary zone electrophoretic separation of peptides and proteins using low pH buffers in modified silica capillaries. Analytical Chemistry 1988, 60 (21), 2322-2328.
51.Paull, B.; King, M., Quantitative capillary zone electrophoresis of inorganic anions. Electrophoresis 2003, 24 (12‐13), 1892-1934.
52.Jorgenson, J. W.; Lukacs, K. D., Zone electrophoresis in open-tubular glass capillaries. Analytical Chemistry 1981, 53 (8), 1298-1302.
53.Heller, C., Principles of DNA separation with capillary electrophoresis. Electrophoresis 2001, 22 (4), 629-643.
54.Rizvi, S. A. A.; Do, D. P.; Saleh, A. M., Fundamentals of micellar electrokinetic chromatography (MEKC). European Journal of Chemistry 2011, 2 (2), 276-281.
55.Hancu, G.; Simon, B.; Rusu, A.; Mircia, E.; Gyéresi, Á., Principles of micellar electrokinetic capillary chromatography applied in pharmaceutical analysis. Advanced Pharmaceutical Bulletin 2013, 3 (1), 1.
56.Muijselaar, P.; Otsuka, K.; Terabe, S., Micelles as pseudo-stationary phases in micellar electrokinetic chromatography. Journal of Chromatography A 1997, 780 (1-2), 41-61.
57.Hansen, S. H.; Gabel-Jensen, C.; El-Sherbiny, D. T. M.; Pedersen-Bjergaard, S., Microemulsion electrokinetic chromatography–or solvent-modified micellar electrokinetic chromatography. Trends in Analytical Chemistry 2001, 20 (11), 614-619.
58.Fuguet, E.; Rafols, C.; Bosch, E.; Abraham, M. H.; Roses, M., Solute–solvent interactions in micellar electrokinetic chromatography: III. Characterization of the selectivity of micellar electrokinetic chromatography systems. Journal of Chromatography A 2002, 942 (1), 237-248.
59.Roig, M.; Bergés, R.; Ventura, R.; Fitch, K.; Morton, A.; Segura, J., Quantification of terbutaline in urine by enzyme-linked immunosorbent assay and capillary electrophoresis after oral and inhaled administrations. Journal of Chromatography B 2002, 768 (2), 315-324.
60.Hillaert, S.; Van den Bossche, W., Optimization and validation of a capillary zone electrophoretic method for the analysis of several angiotensin-II-receptor antagonists. Journal of Chromatography A 2002, 979 (1), 323-333.
61.Wu, Q.; Feng, C.; Zhao, G.; Wang, C.; Wang, Z., Graphene‐coated fiber for solid‐phase microextraction of triazine herbicides in water samples. Journal of Separation Science 2012, 35 (2), 193-199.
62.Mazzola, P. G.; Lopes, A. M.; Hasmann, F. A.; Jozala, A. F.; Penna, T. C.; Magalhaes, P. O.; Rangel‐Yagui, C. O.; Pessoa Jr, A., Liquid–liquid extraction of biomolecules: an overview and update of the main techniques. Journal of Chemical Technology and Biotechnology 2008, 83 (2), 143-157.
63.Sarafraz-Yazdi, A.; Amiri, A., Liquid-phase microextraction. Trends in Analytical Chemistry 2010, 29 (1), 1-14.
64.Psillakis, E.; Kalogerakis, N., Developments in liquid-phase microextraction. TrAC Trends in Analytical Chemistry 2003, 22 (9), 565-574.
65.Luo, W.; Zhu, L.; Deng, J.; Liu, A.; Guo, B.; Tan, W.; Dai, R., Simultaneous analysis of bambuterol and its active metabolite terbutaline enantiomers in rat plasma by chiral liquid chromatography–tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis 2010, 52 (2), 227-231.
66.Żwir-Ferenc, A.; Biziuk, M., Solid Phase Extraction Technique--Trends, Opportunities and Applications. Polish Journal of Environmental Studies 2006, 15 (5).
67.Hennion, M.-C., Solid-phase extraction: method development, sorbents, and coupling with liquid chromatography. Journal of Chromatography A 1999, 856 (1), 3-54.
68.Lavén, M.; Alsberg, T.; Yu, Y.; Adolfsson-Erici, M.; Sun, H., Serial mixed-mode cation-and anion-exchange solid-phase extraction for separation of basic, neutral and acidic pharmaceuticals in wastewater and analysis by high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry. Journal of Chromatography A 2009, 1216 (1), 49-62.
69.Varga, R.; Somogyvári, I.; Eke, Z.; Torkos, K., Determination of antihypertensive and anti-ulcer agents from surface water with solid-phase extraction–liquid chromatography–electrospray ionization tandem mass spectrometry. Talanta 2011, 83 (5), 1447-1454.
70.Kumazawa, T.; Lee, X.-P.; Sato, K.; Suzuki, O., Solid-phase microextraction and liquid chromatography/mass spectrometry in drug analysis. Analytica Chimica Acta 2003, 492 (1), 49-67.
71.Arthur, C. L.; Pawliszyn, J., Solid phase microextraction with thermal desorption using fused silica optical fibers. Analytical Chemistry 1990, 62 (19), 2145-2148.
72.Kataoka, H.; Lord, H. L.; Pawliszyn, J., Applications of solid-phase microextraction in food analysis. Journal of Chromatography A 2000, 880 (1), 35-62.
73.Liu, H.; Dasgupta, P. K., Analytical chemistry in a drop. Solvent extraction in a microdrop. Analytical Chemistry 1996, 68 (11), 1817-1821.
74.Pedersen-Bjergaard, S.; Rasmussen, K. E., Liquid− liquid− liquid microextraction for sample preparation of biological fluids prior to capillary electrophoresis. Analytical Chemistry 1999, 71 (14), 2650-2656.
75.Farajzadeh, M. A.; Sorouraddin, S. M.; Mogaddam, M. R. A., Liquid phase microextraction of pesticides: a review on current methods. Microchimica Acta 2014, 181 (9-10), 829-851.
76.Rezaee, M.; Assadi, Y.; Hosseini, M.-R. M.; Aghaee, E.; Ahmadi, F.; Berijani, S., Determination of organic compounds in water using dispersive liquid–liquid microextraction. Journal of Chromatography A 2006, 1116 (1), 1-9.
77.Nagaraju, D.; Huang, S.-D., Determination of triazine herbicides in aqueous samples by dispersive liquid–liquid microextraction with gas chromatography–ion trap mass spectrometry. Journal of Chromatography A 2007, 1161 (1), 89-97.
78.Zgoła-Grześkowiak, A.; Grześkowiak, T., Dispersive liquid-liquid microextraction. Trends in Analytical Chemistry 2011, 30 (9), 1382-1399.
79.Herrera-Herrera, A. V.; Asensio-Ramos, M.; Hernández-Borges, J.; Rodríguez-Delgado, M. Á., Dispersive liquid-liquid microextraction for determination of organic analytes. Trends in Analytical Chemistry 2010, 29 (7), 728-751.
80.Berijani, S.; Assadi, Y.; Anbia, M.; Hosseini, M.-R. M.; Aghaee, E., Dispersive liquid–liquid microextraction combined with gas chromatography-flame photometric detection: Very simple, rapid and sensitive method for the determination of organophosphorus pesticides in water. Journal of Chromatography A 2006, 1123 (1), 1-9.
81.Farajzadeh, M. A.; Bahram, M.; Jönsson, J. Å., Dispersive liquid–liquid microextraction followed by high-performance liquid chromatography-diode array detection as an efficient and sensitive technique for determination of antioxidants. Analytica Chimica Acta 2007, 591 (1), 69-79.
82.Víctor-Ortega, M. D.; Lara, F. J.; García-Campaña, A. M.; del Olmo-Iruela, M., Evaluation of dispersive liquid–liquid microextraction for the determination of patulin in apple juices using micellar electrokinetic capillary chromatography. Food Control 2013, 31 (2), 353-358.
83.Proelss, H.; Townsend, T. B., Simultaneous liquid-chromatographic determination of five antiarrhythmic drugs and their major active metabolites in serum. Clinical Chemistry 1986, 32 (7), 1311-1317.
84.Seebunrueng, K.; Santaladchaiyakit, Y.; Srijaranai, S., Vortex-assisted low density solvent based demulsified dispersive liquid–liquid microextraction and high-performance liquid chromatography for the determination of organophosphorus pesticides in water samples. Chemosphere 2014, 103, 51-58.
85.Deñola, N. L.; Quiming, N. S.; Saito, Y.; Jinno, K., Simultaneous enantioseparation and sensitivity enhancement of basic drugs using large‐volume sample stacking. Electrophoresis 2007, 28 (19), 3542-3552.
86.Peter Hupe; Gerard Rozing; Doug McManigill; Tom van de Goor; Sally Swedberg; Ulrike Jegle; Martin Verhoef; Lynn Jarke; John Ford; Barbara Krull; Schroeder, a. M., high performance capillary electrophoresis an introduction. 1992.
87.Graul, T. W.; Schlenoff, J. B., Capillaries modified by polyelectrolyte multilayers for electrophoretic separations. Analytical Chemistry 1999, 71 (18), 4007-4013.
88.Liu, Q.; Lin, F.; Hartwick, R. A., Poly (diallyldimethylammonium chloride) as a cationic coating for capillary electrophoresis. Journal of Chromatographic Science 1997, 35 (3), 126-130.
89.Zhang, S.; Li, C.; Song, S.; Feng, T.; Wang, C.; Wang, Z., Application of dispersive liquid–liquid microextraction combined with sweeping micellar electrokinetic chromatography for trace analysis of six carbamate pesticides in apples. Analytical Methods 2010, 2 (1), 54-62.
90.Zhang, S.; Yang, X.; Yin, X.; Wang, C.; Wang, Z., Dispersive liquid–liquid microextraction combined with sweeping micellar electrokinetic chromatography for the determination of some neonicotinoid insecticides in cucumber samples. Food Chemistry 2012, 133 (2), 544-550.
91.Yazdi, A. S.; Razavi, N.; Yazdinejad, S. R., Separation and determination of amitriptyline and nortriptyline by dispersive liquid–liquid microextraction combined with gas chromatography flame ionization detection. Talanta 2008, 75 (5), 1293-1299.
92.Xiong, C.; Ruan, J.; Cai, Y.; Tang, Y., Extraction and determination of some psychotropic drugs in urine samples using dispersive liquid–liquid microextraction followed by high-performance liquid chromatography. Journal of Pharmaceutical and Biomedical Analysis 2009, 49 (2), 572-578.
93.Liang, P.; Xu, J.; Li, Q., Application of dispersive liquid–liquid microextraction and high-performance liquid chromatography for the determination of three phthalate esters in water samples. Analytica Chimica Acta 2008, 609 (1), 53-58.
94.Donthuan, J.; Yunchalard, S.; Srijaranai, S., Vortex‐assisted surfactant‐enhanced‐emulsification liquid–liquid microextraction of biogenic amines in fermented foods before their simultaneous analysis by high‐performance liquid chromatography. Journal of Separation Science 2014, 37 (21), 3164-3173.
95.Melwanki, M. B.; Chen, W.-S.; Bai, H.-Y.; Lin, T.-Y.; Fuh, M.-R., Determination of 7-aminoflunitrazepam in urine by dispersive liquid–liquid microextraction with liquid chromatography–electrospray-tandem mass spectrometry. Talanta 2009, 78 (2), 618-622.
96.Meng, L.; Wang, B.; Luo, F.; Shen, G.; Wang, Z.; Guo, M., Application of dispersive liquid–liquid microextraction and CE with UV detection for the chiral separation and determination of the multiple illicit drugs on forensic samples. Forensic Science International 2011, 209 (1), 42-47.
97.Huang, K.-J.; Wei, C.-Y.; Liu, W.-L.; Xie, W.-Z.; Zhang, J.-F.; Wang, W., Ultrasound-assisted dispersive liquid–liquid microextraction combined with high-performance liquid chromatography-fluorescence detection for sensitive determination of biogenic amines in rice wine samples. Journal of Chromatography A 2009, 1216 (38), 6636-6641.
98.Yan, H.; Wang, H.; Qin, X.; Liu, B.; Du, J., Ultrasound-assisted dispersive liquid–liquid microextraction for determination of fluoroquinolones in pharmaceutical wastewater. Journal of Pharmaceutical and Biomedical Analysis 2011, 54 (1), 53-57.
99.Wen, X.; Yang, Q.; Yan, Z.; Deng, Q., Determination of cadmium and copper in water and food samples by dispersive liquid–liquid microextraction combined with UV–vis spectrophotometry. Microchemical Journal 2011, 97 (2), 249-254.
100.Fortes, S. S.; Barth, T.; Furtado, N. A. J. C.; Pupo, M. T.; de Gaitani, C. M.; de Oliveira, A. R. M., Evaluation of dispersive liquid–liquid microextraction in the stereoselective determination of cetirizine following the fungal biotransformation of hydroxyzine and analysis by capillary electrophoresis. Talanta 2013, 116, 743-752.
101.Scientific, T., LC Columns and Accessories Catalog 2016-2017. 2016-2017
102.Zhou, C.; Tong, S.; Chang, Y.; Jia, Q.; Zhou, W., Ionic liquid‐based dispersive liquid–liquid microextraction with back‐extraction coupled with capillary electrophoresis to determine phenolic compounds. Electrophoresis 2012, 33 (8), 1331-1338.
103.Huang, S.-W.; Hsieh, M.-M.; Chang, S. Y., Sensitive determination of sertraline by capillary electrophoresis with dispersive liquid–liquid microextraction and field-amplified sample stacking. Talanta 2012, 101, 460-464.
104.Li, Y.; Hu, J.; Liu, X.; Fu, L.; Zhang, X.; Wang, X., Dispersive liquid–liquid microextraction followed by reversed phase HPLC for the determination of decabrominated diphenyl ether in natural water. Journal of Separation Science 2008, 31 (13), 2371-2376.
105.Farhadi, K.; Farajzadeh, M. A.; Matin, A. A., Liquid chromatographic determination of benomyl in water samples after dispersive liquid–liquid microextraction. Journal of Separation Science 2009, 32 (14), 24422447.
106.Chou, T.-Y.; Lin, S.-L.; Fuh, M.-R., Determination of phenylurea herbicides in aqueous samples using partitioned dispersive liquid–liquid microextraction. Talanta 2009, 80 (2), 493-498.
107.Soisungnoen, P.; Burakham, R.; Srijaranai, S., Determination of organophosphorus pesticides using dispersive liquid–liquid microextraction combined with reversed electrode polarity stacking mode—micellar electrokinetic chromatography. Talanta 2012, 98, 62-68.
108.Alshana, U.; Göğer, N. G.; Ertaş, N., Dispersive liquid–liquid microextraction combined with field-amplified sample stacking in capillary electrophoresis for the determination of non-steroidal anti-inflammatory drugs in milk and dairy products. Food Chemistry 2013, 138 (2), 890-897.
109.Psillakis, E.; Kalogerakis, N., Application of solvent microextraction to the analysis of nitroaromatic explosives in water samples. Journal of Chromatography A 2001, 907 (1), 211-219.
110.Food; Administration, D., Guidance for industry: bioanalytical method validation. 2001. 2015, 1-22.