臺灣博碩士論文加值系統

使用分散式液液微萃取法(DLLME)結合黏度與場放大樣品堆積技術(FASS)搭配毛細管電泳為一種簡單、快速且靈敏之分析方法，將其用於同時偵測人體尿液樣品中的三種 phenothiazine 類藥物，並以含有 10%(v/v)甘油之 40mM 磷酸鹽水溶液(pH 2.5)作為電泳分離的緩衝溶液。這是因為甘油具有黏性，可大幅改善樣品的解析度與提升其堆積效果。在最佳化條件下，可獲得 1190 至 2067 倍之濃縮倍率，且擁有良好的線性範圍，其介於 0.75~200 nM 之間，而相關係數(r)值為 0.9975~0.9984。此外，根據訊號對雜訊比=3 時，其最低偵測極限(LODS)範圍為 0.15~0.22 nM，且目標分析物的相對標準偏差(RSDs)皆低於 5%。而在尿液樣品中添加 50~200 nM 的三種 Phenothiazine 類藥物，其回收率約有 87.0%~106.8%。藉由本研究所開發的方法，其具有分析時間短、高濃縮倍率、良好的精密度與準確度等優點，可成功應用於測定人體尿液樣品中的 phenothiazine 類藥物。

Dispersive liquid-liquid microextraction followed by viscosity and field-amplifed sample stacking in capillary electrophoresis was determined to be a simple, fast and sensitive analytical method for simultaneously detecting three phenothiazines (promazine, chlorpromazine, and triflupromazine) in a human urine sample. The separation buffer was composed of 40mM phosphate solution (pH 2.5) and 10% (v/v) glycerol. Because glycerol exhibits viscosity, the resolution of the samples and the effect of the stacking could be substantially improved. Under optimized conditions, enrichment factors were obtained that ranged from 1190 to 2067. The proposed method for promazine, chlorpromazine and triflupromazine provided a good linearity that ranged from 0.75 to 200 nM, with correlation coefficients (r) ranging from 0.9975 to 0.9984. The limits of detection based on a signal-to-noise ratio of 3 ranged from 0.15 to 0.22 nM. The relative standard deviations of the target analytes were below 5%. The recoveries of three phenothiazines for urine samples at spiking levels of 50 to 200 nM were 87.0%~106.8%. With the advantages of a short analysis time, high enrichment factors, and high precision and accuracy, the developed method was successfully applied to determine phenothiazine drugs in human urine samples.

目錄
摘要 I
Abstract II
目錄 III
圖目錄 V
表目錄 VI
壹、緒論 1
一、抗精神病藥物簡介 1
1、Phenothiazine藥物 2
2、分析物簡介 3
二、Phenothiazine 藥物分析方法 7
三、毛細管電泳簡介 14
1、毛細管電泳的發展 17
2、毛細管電泳的分離模式 20
2.1毛細管區帶電泳（CZE） 20
2.2微胞電動層析法（MEKC） 22
2.3毛細管電層析法（CEC） 23
2.4毛細管等電聚焦電泳法（CIEF） 24
2.5毛細管凝膠電泳法 (CGE) 24
2.6毛細管等速電泳法（CITP） 25
3、線上樣品濃縮技術 27
3.1場放大樣品堆積法（FASS） 27
3.2大體積樣品堆積法（LVSS） 29
3.3掃集式堆積法 （sweeping stacking） 30
3.4聚合物堆積法（ polymer stacking ） 32
四、萃取方法之簡介 34
4.1 液液萃取法 （LLE） 35
4.2 固相萃取法（SPE） 36
4.3固相微萃取法（SPME） 37
4.4液相微萃取法（LPME） 38
4.5.分散式液液微萃取法 (DLLME) 40
五、研究動機與目的 43
貳、 實驗 44
一、儀器設備 44
二、藥品 46
三、實驗方法 48
3.1 CE-UV 偵測系統 48
3.2儲存溶液的配製 49
3.3緩衝溶液的配製 50
3.4毛細管電泳處理與進樣方式 50
3.5分散式液液微萃取步驟 51
3.6尿液樣品直接分析 52
3.7尿液樣品經分散式液液微萃取後分析 52
參、結果與討論 53
一、毛細管電泳分離條件探討 54
1.1緩衝溶液 pH 值的探討 54
1.2緩衝溶液濃度的探討 57
二、分散式液液微萃取法條件優化 59
2.1萃取劑的選擇 59
2.2分散劑的選擇 63
2.3萃取劑體積的影響 66
2.4分散劑體積的影響 69
2.5溶液 pH 值的影響 72
2.6萃取時間的影響 75
2.7鹽類添加量的影響 77
2.8分散式液液微萃取的最佳條件 79
三、線上樣品濃縮技術 81
3.1甘油含量對堆積的影響 81
3.2進樣時間的探討 84
四、結合分散式液液微萃取與線上濃縮 87
五、方法確效 93
5.1標準樣品直接分析 93
5.2標準樣品經線上濃縮場放大堆積後分析 94
5.3標準樣品經分散式液液微萃取後分析 94
5.4標準樣品結合分散式液液微萃取與線上濃縮 95
5.5靈敏度與濃縮倍率 96
六、生物樣品的應用 102
6.1尿液樣品的分析 102
6.2尿液樣品的定量、靈敏度、精密度與準確度 105
肆、結論 110
參考文獻 111
 
圖目錄
圖 1、Phenothiazine 基本結構 2
圖 2、CE 之平面流型與 HPLC 之拋物線流型 16
圖 3、毛細管區帶電泳(CZE)分離示意圖 21
圖 4、微胞電動層析(MEKC)分離示意圖 23
圖 5、場放大樣品堆積法( FASS )作用機制示意圖 28
圖 6、大體積樣品堆積法( LVSS )作用機制示意圖 30
圖 7、掃集式堆積法(sweeping stacking)作用機制示意圖 31
圖 8、聚合物堆積法(polymer stacking)作用機制示意圖 33
圖 9、毛細管電泳儀器示意圖 48
圖 10、分散式液液微萃取流程圖 51
圖 11、緩衝溶液 pH 值的探討 56
圖 12、緩衝溶液濃度的探討 58
圖 13、萃取劑的選擇 62
圖 14、分散劑的選擇 65
圖 15、萃取劑體積的影響 68
圖 16、分散劑體積的影響 71
圖 17、溶液 pH 值的影響 74
圖 18、萃取時間的影響 76
圖 19、鹽類添加量的影響 78
圖 20、分散式液液微萃取最佳條件的標準層析圖 80
圖 21、甘油含量的探討 83
圖 22、毛細管進樣時間與體積變化量(FASS) 85
圖 23、不同濃縮方式之示意圖 89
圖 24、毛細管進樣時間與體積變化量(DLLME-FASS) 90
圖 25、DLLME 結合線上濃縮所能測到的最低濃度 92
圖 26、尿液樣品與添加分析物後經 DLLME 結合線上濃縮 104
圖 27、尿液樣品經 DLLME 結合線上濃縮所能測到的最低濃度 108




表目錄
表 1、分析物 PMZ、CPZ、TFP 及內標 Perphenazine 之化學結構及其物性 6
表 2、使用不同偵測儀器與樣品前處理應用於 Phenothiazine 類藥物之分析 10
表 3、萃取劑的性質 60
表 4、分散式液液微萃取的最佳條件 79
表 5、場放大樣品堆積技術之秒數對體積的變化量 86
表 6、分散式液液微萃取結合場放大樣品堆積技術之秒數對體積變化量 91
表 7、標準樣品直接分析 97
表 8、標準樣品經線上濃縮場放大堆積後分析 98
表 9、標準樣品經分散式液液微萃取後分析 99
表 10、標準樣品結合分散式液液微萃取與線上濃縮 100
表 11、比較標準樣品經不同分析方法之偵測極限值 101
表 12、比較標準樣品經不同分析方法之濃縮倍率 101
表 13、尿液樣品結合分散式液液微萃取與線上濃縮 107
表 14、尿液樣品經添加後之回收率、準確度與精密度 109

1. Ban, T. A., Fifty years chlorpromazine: a historical perspective. Neuropsychiatric disease and treatment 2007, 3 (4), 495.
2. Jaszczyszyn, A.; Gąsiorowski, K.; Świątek, P.; Malinka, W.; Cieślik-Boczula, K.; Petrus, J.; Czarnik-Matusewicz, B., Chemical structure of phenothiazines and their biological activity. Pharmacological Reports 2012, 64 (1), 16-23.
3. Pluta, K.; Morak-Mlodawska, B.; Jelen, M., Recent progress in biological activities of synthesized phenothiazines. European journal of medicinal chemistry 2011, 46 (8), 3179-89.
4. Cruz-Vera, M.; Lucena, R.; Cardenas, S.; Valcarcel, M., Determination of phenothiazine derivatives in human urine by using ionic liquid-based dynamic liquid-phase microextraction coupled with liquid chromatography. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2009, 877 (1-2), 37-42.
5. Sudeshna, G.; Parimal, K., Multiple non-psychiatric effects of phenothiazines: a review. European journal of pharmacology 2010, 648 (1-3), 6-14.
6. Chen, K.-H.; Lin, C.-E.; Liao, W.-S.; Lin, W.-Y.; Hsiao, Y.-Y., Separation and migration behavior of structurally related phenothiazines in cyclodextrin-modified capillary zone electrophoresis. Journal of Chromatography A 2002, 979 (1), 399-408.
7. Lin, C. E.; Liao, W. S.; Chen, K. H.; Lin, W. Y., Influence of pH on electrophoretic behavior of phenothiazines and determination of pKa values by capillary zone electrophoresis. Electrophoresis 2003, 24 (18), 3154-9.
8. Tanaka, E.; Nakamura, T.; Terada, M.; Shinozuka, T.; Hashimoto, C.; Kurihara, K.; Honda, K., Simple and simultaneous determination for 12 phenothiazines in human serum by reversed-phase high-performance liquid chromatography. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2007, 854 (1-2), 116-20.
9. Lara, F. J.; Garcia-Campana, A. M.; Ales-Barrero, F.; Bosque-Sendra, J. M., Development and validation of a capillary electrophoresis method for the determination of phenothiazines in human urine in the low nanogram per milliliter concentration range using field-amplified sample injection. Electrophoresis 2005, 26 (12), 2418-29.
10. Idris, A. M., On-line coupling of solid-phase extraction, derivatization reaction and spectrophotometry by sequential injection analysis: application to trifluoperazine assay in human urine. Journal of pharmacological and toxicological methods 2007, 56 (3), 330-5.
11. Saracino, M. A.; Amore, M.; Baioni, E.; Petio, C.; Raggi, M. A., Determination of selected phenothiazines in human plasma by solid-phase extraction and liquid chromatography with coulometric detection. Analytica chimica acta 2008, 624 (2), 308-16.
12. Lehmann, H. E.; Ban, T. A., The history of the psychopharmacology of schizophrenia. Canadian Journal of Psychiatry 1997, 42 (2), 152-162.
13. Ohlow, M. J.; Moosmann, B., Phenothiazine: the seven lives of pharmacology's first lead structure. Drug discovery today 2011, 16 (3-4), 119-31.
14. Kapur, S.; Mizrahi, R.; Li, M., From dopamine to salience to psychosis--linking biology, pharmacology and phenomenology of psychosis. Schizophrenia research 2005, 79 (1), 59-68.
15. Lara, F. J.; García-Campaña, A. M.; Alés-Barrero, F.; Bosque-Sendra, J. M., Determination of thiazinamium, promazine and promethazine in pharmaceutical formulations using a CZE method. Analytica chimica acta 2005, 535 (1-2), 101-108.
16. Lara, F. J.; Garcia-Campana, A. M.; Gamiz-Gracia, L.; Bosque-Sendra, J. M.; Ales-Barrero, F., Determination of phenothiazines in pharmaceutical formulations and human urine using capillary electrophoresis with chemiluminescence detection. Electrophoresis 2006, 27 (12), 2348-59.
17. Larsimont, V.; Meins, J.; Fieger-Büschges, H.; Blume, H., Validated high-performance liquid chromatographic assay for the determination of promazine in human plasma: application to pharmacokinetic studies. Journal of Chromatography B: Biomedical Sciences and Applications 1998, 719 (1), 222-226.
18. Schulz, M.; Schmoldt, A., Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics. Die Pharmazie-An International Journal of Pharmaceutical Sciences 2003, 58 (7), 447-474.
19. Kandagal, P. B.; Shaikh, S. M. T.; Manjunatha, D. H.; Seetharamappa, J.; Nagaralli, B. S., Spectroscopic studies on the binding of bioactive phenothiazine compounds to human serum albumin. Journal of Photochemistry and Photobiology A: Chemistry 2007, 189 (1), 121-127.
20. Dziomba, S.; Kowalski, P.; Baczek, T., Micelle to solvent stacking of tricyclic psychiatric drugs in capillary electrophoresis. Journal of pharmaceutical and biomedical analysis 2012, 62, 149-54.
21. Persike, M.; Karas, M., Rapid simultaneous quantitative determination of different small pharmaceutical drugs using a conventional matrix-assisted laser desorption/ionization time-of-flight mass spectrometry system. Rapid communications in mass spectrometry : RCM 2009, 23 (22), 3555-62.
22. Quirino, J. P.; Aranas, A. T., On-line sample concentration via micelle to solvent stacking of cations prepared with aqueous organic solvents in capillary electrophoresis. Electrophoresis 2012, 33 (14), 2167-75.
23. Rasanen, I.; Kontinen, I.; Nokua, J.; Ojanperä, I.; Vuori, E., Precise gas chromatography with retention time locking in comprehensive toxicological screening for drugs in blood. Journal of Chromatography B 2003, 788 (2), 243-250.
24. Reubsaet, J. L. E.; Pedersen-Bjergaard, S., Screening for central nervous system-stimulating drugs in human plasma by liquid chromatography with mass spectrometric detection. Journal of Chromatography A 2004, 1031 (1-2), 203-211.
25. Le, D. C.; Morin, C. J.; Beljean, M.; Siouffi, A. M.; Desbène, P. L., Electrophoretic separations of twelve phenothiazines and N-demethyl derivatives by using capillary zone electrophoresis and micellar electrokinetic chromatography with non ionic surfactant. Journal of Chromatography A 2005, 1063 (1-2), 235-240.
26. Choi, H. N.; Cho, S.-H.; Park, Y.-J.; Lee, D. W.; Lee, W.-Y., Sol–gel-immobilized Tris(2,2′-bipyridyl)ruthenium(II) electrogenerated chemiluminescence sensor for high-performance liquid chromatography. Analytica chimica acta 2005, 541 (1-2), 47-54.
27. Madej, K.; Kala, M.; Woźniakiewicz, M., LC and non-aqueous CE determination of phenothiazines in autopsy samples. Chromatographia 2005, 62 (9-10), 533-538.
28. Madej, K.; Woźniakiewicz, M.; Kała, M., Method for screening and quantification of seven phenothiazines in whole blood samples by non-aqueous capillary electrophoresis. Chromatographia 2005, 61 (5-6), 259-263.
29. Li, J.; Zhao, F.; Ju, H., Simultaneous determination of psychotropic drugs in human urine by capillary electrophoresis with electrochemiluminescence detection. Analytica chimica acta 2006, 575 (1), 57-61.
30. Sobhi, H. R.; Yamini, Y.; Abadi, R. H., Extraction and determination of trace amounts of chlorpromazine in biological fluids using hollow fiber liquid phase microextraction followed by high-performance liquid chromatography. Journal of pharmaceutical and biomedical analysis 2007, 45 (5), 769-74.
31. Xiao, Q.; Hu, B., Hollow fiber-liquid phase microextraction combined with gas chromatography for the determination of phenothiazine drugs in urine. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2010, 878 (19), 1599-604.
32. Saar, E.; Gerostamoulos, D.; Drummer, O. H.; Beyer, J., Identification and quantification of 30 antipsychotics in blood using LC-MS/MS. Journal of mass spectrometry : JMS 2010, 45 (8), 915-25.
33. Kumazawa, T.; Hasegawa, C.; Uchigasaki, S.; Lee, X. P.; Suzuki, O.; Sato, K., Quantitative determination of phenothiazine derivatives in human plasma using monolithic silica solid-phase extraction tips and gas chromatography-mass spectrometry. Journal of chromatography. A 2011, 1218 (18), 2521-7.
34. da Fonseca, B. M.; Moreno, I. E.; Barroso, M.; Costa, S.; Queiroz, J. A.; Gallardo, E., Determination of seven selected antipsychotic drugs in human plasma using microextraction in packed sorbent and gas chromatography-tandem mass spectrometry. Analytical and bioanalytical chemistry 2013, 405 (12), 3953-63.
35. Kohlrausch, F., Ueber Concentrations-Verschiebungen durch Electrolyse im Inneren von Lösungen und Lösungsgemischen. Annalen der Physik 1897, 298 (10), 209-239.
36. Tiselius, A., A new apparatus for electrophoretic analysis of colloidal mixtures. Transactions of the Faraday Society 1937, 33 (0), 524-531.
37. Hjertén, S., Free zone electrophoresis. Chromatographic Reviews 1967, 9 (2), 122-219.
38. Mikkers, F. E. P.; Everaerts, F. M.; Verheggen, T. P. E. M., High-performance zone electrophoresis. Journal of Chromatography A 1979, 169 (0), 11-20.
39. Virtanen, R., Zone Electrophoresis in a Narrow-bore Tube Employing Potentiometric Detection: A Theoretical and Experimental Study. Finnish Acad. of Techn. Sciences: 1974.
40. Jorgenson, J. W.; Lukacs, K. D., High-resolution separations based on electrophoresis and electroosmosis. Journal of Chromatography A 1981, 218 (0), 209-216.
41. Jorgenson, J. W.; Lukacs, K. D., Zone electrophoresis in open-tubular glass capillaries. Analytical Chemistry 1981, 53 (8), 1298-1302.
42. Jorgenson, J.; Lukacs, K., Capillary zone electrophoresis. Science 1983, 222 (4621), 266-272.
43. Terabe, S.; Otsuka, K.; Ichikawa, K.; Tsuchiya, A.; Ando, T., Electrokinetic separations with micellar solutions and open-tubular capillaries. Analytical Chemistry 1984, 56 (1), 111-113.
44. Terabe, S.; Otsuka, K.; Ando, T., Electrokinetic chromatography with micellar solution and open-tubular capillary. Analytical Chemistry 1985, 57 (4), 834-841.
45. Tsuda, T., Electrochromatography using high applied voltage. Analytical Chemistry 1987, 59 (3), 521-523.
46. Hjertén, S.; Zhu, M.-d., Adaptation of the equipment for high-performance electrophoresis to isoelectric focusing. Journal of Chromatography A 1985, 346 (0), 265-270.
47. Cohen, A. S.; Karger, B. L., High-performance sodium dodecyl sulfate polyacrylamide gel capillary electrophoresis of peptides and proteins. Journal of Chromatography A 1987, 397 (0), 409-417.
48. Touchstone, J. C., History of chromatography. Journal of Liquid Chromatography & Related Technologies 1993, 16 (8), 1647-1665.
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. 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.
53. 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.
54. Muijselaar, P.; Otsuka, K.; Terabe, S., Micelles as pseudo-stationary phases in micellar electrokinetic chromatography. Journal of Chromatography A 1997, 780 (1), 41-61.
55. Bartle, K. D.; Myers, P., Theory of capillary electrochromatography. Journal of Chromatography A 2001, 916 (1–2), 3-23.
56. Eeltink, S.; Rozing, G. P.; Kok, W. T., Recent applications in capillary electrochromatography. Electrophoresis 2003, 24 (22-23), 3935-3961.
57. Rodriguez-Diaz, R.; Wehr, T.; Zhu, M., Capillary isoelectric focusing. Electrophoresis 1997, 18 (12-13), 2134-2144.
58. Shen, Y.; Berger, S. J.; Anderson, G. A.; Smith, R. D., High-Efficiency Capillary Isoelectric Focusing of Peptides. Analytical Chemistry 2000, 72 (9), 2154-2159.
59. Kilár, F., Recent applications of capillary isoelectric focusing. Electrophoresis 2003, 24 (22-23), 3908-3916.
60. Thormann, W.; Kilár, F., High-resolution dynamic computer simulation analysis of the behavior of sample components with pI values outside the pH gradient established by carrier ampholyte CIEF. Electrophoresis 2013, 34 (5), 716-724.
61. Zhang, J.; Fang, Y.; Hou, J. Y.; Ren, H. J.; Jiang, R.; Roos, P.; Dovichi, N. J., Use of Non-Cross-Linked Polyacrylamide for Four-Color DNA Sequencing by Capillary Electrophoresis Separation of Fragments up to 640 Bases in Length in Two Hours. Analytical Chemistry 1995, 67 (24), 4589-4593.
62. Barron, A. E.; Sunada, W. M.; Blanch, H. W., The effects of polymer properties on DNA separations by capillary electrophoresis in uncross-linked polymer solutions. Electrophoresis 1996, 17 (4), 744-757.
63. Zhu, Z.; Lu, J. J.; Liu, S., Protein separation by capillary gel electrophoresis: A review. Analytica chimica acta 2012, 709 (0), 21-31.
64. Beckers, J. L.; Everaerts, F. M., Isotachophoresis with two leading ions and migration behaviour in capillary zone electrophoresis: II. Migration behaviour in capillary zone electrophoresis. Journal of Chromatography A 1990, 508 (0), 19-26.
65. Mazereeuw, M.; Tjaden, U. R.; Reinhoud, N. J., Single Capillary Isotachophoresis—Zone Electrophoresis: Current Practice and Prospects, A Review. Journal of Chromatographic Science 1995, 33 (12), 686-697.
66. Křivánková, L.; Boček, P., Synergism of capillary isotachophoresis and capillary zone electrophoresis. Journal of Chromatography B: Biomedical Sciences and Applications 1997, 689 (1), 13-34.
67. Muijselaar, P. G. H. M.; Claessens, H. A.; Cramers, C. A., Determination of structurally related phenothiazines by capillary zone electrophoresis and micellar electrokinetic chromatography. Journal of Chromatography A 1996, 735 (1–2), 395-402.
68. Osbourn, D. M.; Weiss, D. J.; Lunte, C. E., On-line preconcentration methods for capillary electrophoresis. Electrophoresis 2000, 21 (14), 2768-2779.
69. Manetto, G.; Tagliaro, F.; Crivellente, F.; Pascali, V. L.; Marigo, M., Field-amplified sample stacking — capillary zone electrophoresis applied to the analysis of opiate drugs in hair. Electrophoresis 2000, 21 (14), 2891-2898.
70. Breadmore, M. C.; Shallan, A. I.; Rabanes, H. R.; Gstoettenmayr, D.; Abdul Keyon, A. S.; Gaspar, A.; Dawod, M.; Quirino, J. P., Recent advances in enhancing the sensitivity of electrophoresis and electrochromatography in capillaries and microchips (2010–2012). Electrophoresis 2013, 34 (1), 29-54.
71. Kitagawa, F.; Otsuka, K., Recent applications of on-line sample preconcentration techniques in capillary electrophoresis. Journal of Chromatography A 2014, 1335 (0), 43-60.
72. Chien, R. L.; Burgi, D. S., Sample stacking of an extremely large injection volume in high-performance capillary electrophoresis. Analytical Chemistry 1992, 64 (9), 1046-1050.
73. Quirino, J. P.; Terabe, S., Sample stacking of cationic and anionic analytes in capillary electrophoresis. Journal of Chromatography A 2000, 902 (1), 119-135.
74. Zhu, Z.; Zhang, L.; Marimuthu, A.; Yang, Z., Large-volume sample stacking combined with separation by 2-hydroxypropyl-β-cyclodextrin for analysis of isoxyzolylpenicillins by capillary electrophoresis. Electrophoresis 2003, 24 (17), 3089-3096.
75. Zhu, Z.; Zhang, L.; Marimuthu, A.; Yang, Z., Large-volume sample stacking for analysis of ethylenediaminetetraacetic acid by capillary electrophoresis. Electrophoresis 2002, 23 (17), 2880-2887.
76. Shih, C.-M.; Lin, C.-H., Full-capillary sample stacking/sweeping-MEKC for the separation of naphthalene-2,3-dicarboxaldehyde-derivatized tryptophan and isoleucine. Electrophoresis 2005, 26 (18), 3495-3499.
77. Zhu, Z. f.; Yan, N.; Zhou, X.; Zhou, L.; Chen, X., Simultaneous enrichment and separation of neutral and anionic analytes through combining large volume sample stacking with sweeping in CE. Journal of separation science 2009, 32 (20), 3481-3488.
78. Tseng, W.-L.; Chang, H.-T., On-Line Concentration and Separation of Proteins by Capillary Electrophoresis Using Polymer Solutions. Analytical Chemistry 2000, 72 (20), 4805-4811.
79. Hsieh, M. M.; Tseng, W. L.; Chang, H. T., On‐column preconcentration and separation of DNA fragments using polymer solutions in the presence of electroosmotic flow. Electrophoresis 2000, 21 (14), 2904-2910.
80. 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.
81. 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.
82. Hsieh, M.-M.; Chang, H.-T., Discontinuous electrolyte systems for improved detection of biologically active amines and acids by capillary electrophoresis with laser-induced native fluorescence detection. Electrophoresis 2005, 26 (1), 187-195.
83. Hsieh, M.-M.; Lin, E.-P.; Huang, S.-W., On-line concentration and separation of cationic and anionic neurochemicals by capillary electrophoresis with UV absorption detection. Talanta 2012, 88 (0), 638-645.
84. Mazzola, P. G.; Lopes, A. M.; Hasmann, F. A.; Jozala, A. F.; Penna, T. C. V.; 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 & Biotechnology 2008, 83 (2), 143-157.
85. Borges, N. C.; Rezende, V. M.; Santana, J. M.; Moreira, R. P.; Moreira, R. F.; Moreno, P.; Borges, D. C.; Donato, J. L.; Moreno, R. A., Chlorpromazine quantification in human plasma by UPLC-electrospray ionization tandem mass spectrometry. Application to a comparative pharmacokinetic study. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2011, 879 (31), 3728-34.
86. Sarafraz-Yazdi, A.; Amiri, A., Liquid-phase microextraction. TrAC Trends in Analytical Chemistry 2010, 29 (1), 1-14.
87. Psillakis, E.; Kalogerakis, N., Developments in liquid-phase microextraction. TrAC Trends in Analytical Chemistry 2003, 22 (9), 565-574.
88. Żwir-Ferenc, A.; Biziuk, M., Solid phase extraction technique–trends, opportunities and applications. Polish Journal of Environmental Studies 2006, 15 (5), 677-690.
89. Sampedro, M. C.; Unceta, N.; Gomez-Caballero, A.; Callado, L. F.; Morentin, B.; Goicolea, M. A.; Meana, J. J.; Barrio, R. J., Screening and quantification of antipsychotic drugs in human brain tissue by liquid chromatography-tandem mass spectrometry: application to postmortem diagnostics of forensic interest. Forensic science international 2012, 219 (1-3), 172-8.
90. 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 (1-2), 49-67.
91. Kataoka, H.; Lord, H. L.; Pawliszyn, J., Applications of solid-phase microextraction in food analysis. Journal of Chromatography A 2000, 880 (1–2), 35-62.
92. Shinmen, N.; Lee, X.-P.; Kumazawa, T.; Hasegawa, C.; Ishiwata, Y.; Sato, K.; Seno, H.; Suzuki, O., Simultaneous Determination of Some Phenothiazine Derivatives in Human Blood by Headspace Solid-Phase Microextraction and Gas Chromatography with Nitrogen-Phosphorus Detection. Journal of AOAC International 2008, 91 (6), 1354-1362.
93. Liu, H.; Dasgupta, P. K., Analytical Chemistry in a Drop. Solvent Extraction in a Microdrop. Analytical Chemistry 1996, 68 (11), 1817-1821.
94. 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.
95. Rezaee, M.; Assadi, Y.; Milani Hosseini, M.-R.; Aghaee, E.; Ahmadi, F.; Berijani, S., Determination of organic compounds in water using dispersive liquid–liquid microextraction. Journal of Chromatography A 2006, 1116 (1–2), 1-9.
96. 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 (1–2), 89-97.
97. Berijani, S.; Assadi, Y.; Anbia, M.; Milani Hosseini, M.-R.; 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.
98. 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.
99. Shamsipur, M.; Fattahi, N., Extraction and determination of opium alkaloids in urine samples using dispersive liquid–liquid microextraction followed by high-performance liquid chromatography. Journal of Chromatography B 2011, 879 (28), 2978-2983.
100. 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.
101. 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.
102. 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), 544-50.
103. 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), 572-8.
104. 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), 53-8.
105. 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. J Sep Sci 2014, 37 (21), 3164-73.
106. Fortes, S. S.; Barth, T.; Furtado, N. A.; Pupo, M. T.; de Gaitani, C. M.; de Oliveira, A. R., 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, 743-52.
107. 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.
108. 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), 618-22.
109. 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 (1-3), 42-7.
110. 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), 1293-9.
111. 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), 1331-8.
112. 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, 460-4.
113. 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. J Sep Sci 2008, 31 (13), 2371-6.
114. 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.
115. Thompson, J. W.; Kaiser, T. J.; Jorgenson, J. W., Viscosity measurements of methanol–water and acetonitrile–water mixtures at pressures up to 3500 bar using a novel capillary time-of-flight viscometer. Journal of Chromatography A 2006, 1134 (1–2), 201-209.
116. Guidance for Industry Bioanalytical Method Validation. Food and Drug Administration 2013, 1-28.