臺灣博碩士論文加值系統

使用分散式液液微萃取法（DLLME）結合黏度與聚合物堆積技術（polymer stacking）搭配毛細管電泳是一種簡單且具靈敏度的分析方法，將此法用於檢測人體尿液及血清中的RS-Warfarin及其代謝物RS-7-OH- Warfarin，並使用含有5 mM DM-β-CD及0.5 %（w/v）PEO之200 mM Tris-Borate（pH 8.5）作為分離的電泳緩衝溶液。實驗使用PEO作為堆積試劑，因其具有黏性且與分析物會形成分子間作用力，可有效輔助堆積效果並大幅提升偵測靈敏度。在最佳化條件下，可獲得1758至1859倍的濃縮倍率，且具有良好的濃度線性範圍，介於1.5~600.0 nM之間，而相關係數r值為0.9952~ 0.9962。除此之外，根據在訊號/雜訊比（S/N）=3時，最低偵測極限（LODs）範圍為0.33~0.38 nM，且目標分析物的相對標準偏差（RSDs）皆低於5 %（n=12）。在實際樣品的部分，尿液樣品中添加50~200 nM的兩種目標分析物，其回收率約有91.9~106.2 %；而血清樣品添加0.05~2 μM的兩種目標分析物，回收率約有92.4~109.4 %。藉由本研究所開發的方法，具有高濃縮倍率、良好的準確度與精密度等優點，可成功應用於測定尿液及血清中的藥物。

Dispersive liquid–liquid microextraction followed by viscosity and polymer stacking in capillary electrophoresis was determined to be a simple and sensitive analytical method for detecting RS-Warfarin and its metabolite RS-7-OH-Warfarin in human urine and serum. The separation buffer comprised 200 mM Tris-borate (pH 8.5) and 0.5% (w/v) poly(ethylene oxide) (PEO). Because PEO exhibits viscosity and an intermolecular force interaction between PEO and analytes, the effect of the polymer tacking and detection sensitivity could be substantially improved. The enrichment factors obtained under optimized conditions ranged from 1758 to 1859. The proposed method for detecting RS-Warfarin and RS-7-OH-Warfarin provided a strong linearity that ranged from 1.5 to 600.0 nM, with correlation coefficients (r) ranging from 0.9952 to 0.9962. The detection limits based on a signal-to-noise ratio of 3 ranged from 0.33 to 0.38 nM. The relative standard deviations of the target analytes were all below 5% (n = 12). In the real sample, the recoveries of analytes for the urine sample at spiking levels of 50–200 nM and the serum sample at spiking levels of 0.05–2 μM were in the ranges of 91.9%–106.2% and 96.5%–103.5%, respectively. With the advantages of high enrichment factors and high accuracy and precision, the developed method was successfully applied to determine drugs in
urine and serum.

摘要 I
Abstract II
目錄 III
圖目錄 V
表目錄 VII
壹、緒論 1
一、抗凝血劑簡介 1
1.1 分析物簡介 2
二、藥物分析方法 5
三、環糊精簡介 14
四、毛細管電泳簡介 18
五、毛細管電泳的分離模式 21
5.1 毛細管區帶電泳（CZE） 21
5.2 微胞電動層析法（MEKC） 22
六、線上樣品濃縮技術 25
6.1 場放大樣品堆積法（FASS） 26
6.2 大體積樣品堆積法（LVSS） 27
6.3 掃集式堆積法（Sweeping stacking） 29
6.4 聚合物堆積法（polymer stacking） 30
七、萃取方法之簡介 32
7.1 液-液萃取法（LLE） 33
7.2 固相萃取法（SPE） 34
7.3 固相微萃取法（SPME） 36
7.4 液相微萃取法（LPME） 37
7.5 分散式液液微萃取法（DLLME） 38
八、研究動機與目的 41
貳、實驗 42
一、儀器設備 42
二、實驗藥品 43
三、實驗方法 46
3.1 CE-UV偵測系統 46
3.2 儲存溶液的配製 47
3.3 緩衝溶液的配製 48
3.4 毛細管電泳處理與進樣方式 48
3.5 分散式液液微萃取步驟 49
3.6 尿液樣品直接分析 50
3.7 尿液樣品經分散式液液微萃取後分析 50
3.8 血清樣品直接分析 50
3.9 血清樣品經分散式液液微萃取後分析 51
參、結果與討論 52
一、毛細管電泳分離條件探討 53
1.1 緩衝溶液對於分離的影響 54
1.2 環糊精對於分離的影響 56
1.3 緩衝溶液pH值對於分離的影響 64
1.4 緩衝溶液離子強度對於分離的影響 67
二、分散式液液微萃取法（DLLME）條件探討 69
2.1 萃取劑的選擇 70
2.2 萃取劑體積的影響 74
2.3 分散劑的選擇 77
2.4 分散劑體積的影響 80
2.5 溶液pH值對於萃取效率的影響 83
2.6 萃取時間的影響 86
2.7 鹽類添加量的影響 89
2.8 分散式液液微萃取的最佳條件 91
三、線上樣品濃縮技術 93
3.1 PEO含量對於堆積的影響 93
3.2 進樣時間的探討 96
四、結合分散式液液微萃取與線上濃縮 99
五、方法確效 105
5.1 標準樣品直接分析 105
5.2 標準樣品經線上濃縮堆積後分析 106
5.3 標準樣品經分散式液液微萃取後分析 106
5.4 標準樣品結合分散式液液微萃取與線上濃縮後分析 107
5.5 靈敏度與濃縮倍率 108
六、生物樣品的應用 114
6.1 尿液樣品的分析 114
6.2 尿液樣品的定量、靈敏度、精密度與準確度 117
6.3 血清樣品的分析 122
6.4 血清樣品的定量、靈敏度、精密度與準確度 126
肆、結論 131
參考文獻 132

圖目錄
圖1、Warfarin及其代謝物之結構 3
圖2、環糊精杯狀結構示意圖 16
圖3、環糊精結構示意圖（A）α-CD（B）β-CD（C）γ-CD 16
圖4、毛細管電泳之平面流型與HPLC之拋物線流型 20
圖5、毛細管區帶電泳法（CZE）分離示意圖 22
圖6、微胞電動層析（MEKC）分離示意圖 24
圖7、場放大樣品堆積法（FASS）作用機制示意圖 27
圖8、大體積樣品堆積法（LVSS）作用機制示意圖 28
圖9、掃集式堆積法（Sweeping stacking）作用機制示意圖 30
圖10、聚合物堆積法（polymer stacking）作用機制示意圖 31
圖11、固相萃取法（SPE）流程圖 35
圖12、毛細管電泳儀器示意圖 46
圖13、分散式液液微萃取流程圖 49
圖14、緩衝溶液的探討 55
圖15、緩衝溶液中添加不同濃度之β-CD進行探討 57
圖16、緩衝溶液中添加不同濃度之HP-β-CD進行探討 58
圖17、緩衝溶液中添加不同濃度之DM-β-CD進行探討 59
圖18、緩衝溶液中添加不同濃度之HP-α-CD進行探討 60
圖19、不同種類及濃度之環糊精最佳層析圖 61
圖20、不同種類及濃度（mM）的環糊精對分析物之解析度示意 63
圖21、緩衝溶液pH值的探討 66
圖22、緩衝溶液離子強度的探討 68
圖23、萃取劑的選擇 73
圖24、萃取劑體積的影響 76
圖25、分散劑的選擇 79
圖26、分散劑的體積 82
圖27、溶液pH值的影響 85
圖28、萃取時間的影響 88
圖29、鹽類添加量的影響 90
圖30、分散式液液微萃取最佳條件的標準層析圖 92
圖31、PEO含量探討 95
圖32、毛細管進樣時間與體積變化量 97
圖33、分析物訊號面積 98
圖34、不同濃縮方式之示意圖 101
圖35、毛細管進樣時間與體積變化量（DLLME-polymer stacking） 102
圖36、分析物訊號面積 103
圖37、DLLME結合線上濃縮所能偵測之最低濃度 104
圖38、尿液樣品與添加分析物後經DLLME結合線上濃縮 116
圖39、尿液樣品經DLLME結合線上濃縮所能測到的最低濃度 120
圖40、血清樣品與添加分析物後經DLLME結合線上濃縮 125
圖41、血清樣品經DLLME結合線上濃縮所能測到的最低濃度 129

表目錄
表1、分析物之化學結構與物理性質 5
表2、使用不同偵測器與樣品前處理應用於Warfarin及其多種代謝物之分析 10
表3、α、β、γ環糊精的性質 17
表4、微胞電動層析法常用的界面活性劑 24
表5、四種環糊精對R、S-WAR與R、S-7-OH的分離解析度 63
表6、萃取劑的性質 71
表7、分散劑的極性 77
表8、分散式液液微萃取的最佳條件 91
表9、標準樣品直接分析 109
表10、標準樣品經線上濃縮堆積後分析 110
表11、標準樣品經分散式液液微萃取後分析 111
表12、標準樣品經分散式液液微萃取與線上濃縮後分析 112
表13、比較標準樣品經不同分析方法之偵測極限值 113
表14、比較標準樣品經不同分析方法之濃縮倍率 113
表15、尿液樣品結合分散式液液微萃取與線上濃縮 119
表16、尿液樣品經添加後之回收率、精密度與準確度 121
表17、血清樣品結合分散式液液微萃取與線上濃縮 128
表18、血清樣品經添加後之回收率、精密度與準確度 130

1.McLean, J., The discovery of heparin. Circulation 1959, 19 (1), 75-78.
2.Mc, L. J.; Meyer, B. M.; Griffith, J. M., Heparin in subacute bacterial endocarditis: Report of cases and critical review of literature. Journal of the American Medical Association 1941, 117 (22), 1870-1875.
3.Campbell, H. A.; Link, K. P., Studies on the hemorrhagic sweet clover disease. 4. The isolation and crystallisation of the hemorrhagic agent. Journal of Biological Chemistry 1941, 138, 21-33.
4.Nowak, P.; Garnysz, M.; Mitoraj, M. P.; Sagan, F.; Woźniakiewicz, M.; Kościelniak, P., Analytical aspects of achiral and cyclodextrin-mediated capillary electrophoresis of warfarin and its two main derivatives assisted by theoretical modeling. Journal of Chromatography A 2015, 1377, 106-113.
5.Denooz, R.; Douamba, Z.; Charlier, C., Fatal intoxications by acenocoumarol, phenprocoumon and warfarin: Method validation in blood using the total error approach. Journal of Chromatography B 2009, 877 (23), 2344-2348.
6.Huang, C.; Yang, J.; Du, Y.; Miao, L., Measurement of free concentrations of highly protein-bound warfarin in plasma by ultra performance liquid chromatography–tandem mass spectrometry and its correlation with the international normalized ratio. Clinica Chimica Acta 2008, 393 (2), 85-89.
7.de Armas, G.; Miró, M.; Estela, J. M.; Cerdà, V. c., Multisyringe flow injection spectrofluorimetric determination of warfarin at trace levels with on-line solid-phase preconcentration. Analytica Chimica Acta 2002, 467 (1–2), 13-23.
8.Banfield, C.; O'reilly, R.; Chan, E.; Rowland, M., Phenylbutazone‐warfarin interaction in man: further stereochemical and metabolic considerations. British journal of clinical pharmacology 1983, 16 (6), 669-675.
9.Yamazaki, H.; Shimada, T., Human liver cytochrome P450 enzymes involved in the 7-hydroxylation of R-and S-warfarin enantiomers. Biochemical pharmacology 1997, 54 (11), 1195-1203.
10.Reilly, R. A., Studies on the optical enantiomorphs of warfarin in man. Clinical Pharmacology & Therapeutics 1974, 16 (2), 348-354.
11.Lewis, R. J.; Trager, W. F., Warfarin metabolism in man: identification of metabolites in urine. Journal of Clinical investigation 1970, 49 (5), 907.
12.Rettie, A. E.; Korzekwa, K. R.; Kunze, K. L.; Lawrence, R. F.; Eddy, A. C.; Aoyama, T.; Gelboin, H. V.; Gonzalez, F. J.; Trager, W. F., Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chemical research in toxicology 1992, 5 (1), 54-59.
13.Lang, D.; Böcker, R., Highly sensitive and specific high-performance liquid chromatographic analysis of 7-hydroxywarfarin, a marker for human cytochrome P-4502C9 activity. Journal of Chromatography B: Biomedical Sciences and Applications 1995, 672 (2), 305-309.
14.Hirsh, J.; Dalen, J. E.; Anderson, D. R.; Poller, L.; Bussey, H.; Ansell, J.; Deykin, D., Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest Journal 2001, 119 (1_suppl), 8S-21S.
15.Lacy, C.; Armstrong, L.; Goldman, M., Drug information handbook 2002-2003. Lexi-comp: 2002.
16.Fasco, M.; Hildebrandt, E.; Suttie, J., Evidence that warfarin anticoagulant action involves two distinct reductase activities. Journal of Biological Chemistry 1982, 257 (19), 11210-11212.
17.Urien, S.; Albengres, E.; Pinquier, J. L.; Tillement, J. P., Role of alpha‐1 acid glycoprotein, albumin, and nonesterified fatty acids in serum binding of apazone and warfarin. Clinical Pharmacology & Therapeutics 1986, 39 (6), 683-689.
18.O'Reilly, R.; Welling, P.; Wagner, J., Pharmacokinetics of warfarin following intravenous administration to man. Thrombosis et diathesis haemorrhagica 1970, 25 (1), 178-186.
19.Tummel, K., Design and optimization of dosage regimens: pharmacokinetic data. Goodman & Gilman's the pharmacological basis of therapeutics 2001.
20.Brigden, M. L.; Kay, C.; Le, A.; Graydon, C.; McLeod, B., Audit of the frequency and clinical response to excessive oral anticoagulation in an out-patient population. American journal of hematology 1998, 59 (1), 22-27.
21.Hylek, E. M.; Heiman, H.; Skates, S. J.; Sheehan, M. A.; Singer, D. E., Acetaminophen and other risk factors for excessive warfarin anticoagulation. Jama 1998, 279 (9), 657-662.
22.Booth, S. L.; Centurelli, M. A., Vitamin K: a practical guide to the dietary management of patients on warfarin. Nutrition reviews 1999, 57 (9), 288-296.
23.O'Reilly, R. A., Lack of effect of fortified wine ingested during fasting and anticoagulant therapy. Archives of internal medicine 1981, 141 (4), 458-459.
24.Bauman, J. L.; Sanoski, C. A.; Chan, L.-n., Pharmacokinetic and Pharmacodynamic Drug Interactions with Antiarrhythmic Agents. Cardiology in Review 1997, 5 (6), 292-304.
25.Heimark, L. D.; Wienkers, L.; Kunze, K.; Gibaldi, M.; Eddy, A. C.; Trager, W. F.; O'Reilly, R. A.; Goulart, D. A., The mechanism of the interaction between amiodarone and warfarin in humans. Clinical Pharmacology & Therapeutics 1992, 51 (4), 398-407.
26.Osman, A.; Arbring, K.; Lindahl, T. L., A new high-performance liquid chromatographic method for determination of warfarin enantiomers. Journal of Chromatography B 2005, 826 (1), 75-80.
27.Jin, M. c.; Chen, X. h.; Chen, H. p., Determination of Warfarin and Coumatetralyl in Serum by HPLC Coupled with Electrospray Ionization Mass Spectrometry. Journal of Liquid Chromatography & Related Technologies 2006, 29 (18), 2641-2650.
28.Malakova, J.; Pavek, P.; Svecova, L.; Jokesova, I.; Zivny, P.; Palicka, V., New high-performance liquid chromatography method for the determination of (R)-warfarin and (S)-warfarin using chiral separation on a glycopeptide-based stationary phase. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2009, 877 (27), 3226-30.
29.Zuo, Z.; Wo, S. K.; Lo, C. M.; Zhou, L.; Cheng, G.; You, J. H., Simultaneous measurement of S-warfarin, R-warfarin, S-7-hydroxywarfarin and R-7-hydroxywarfarin in human plasma by liquid chromatography-tandem mass spectrometry. Journal of pharmaceutical and biomedical analysis 2010, 52 (2), 305-10.
30.Gareil, P.; Gramond, J.; Guyon, F., Separation and determination of warfarin enantiomers in human plasma samples by capillary zone electrophoresis using a methylated β-cyclodextrin-containing electrolyte. Journal of Chromatography B: Biomedical Sciences and Applications 1993, 615 (2), 317-325.
31.Wang, M.; Cai, Z.; Xu, L., Coupling of acetonitrile deproteinization and salting-out extraction with acetonitrile stacking in chiral capillary electrophoresis for the determination of warfarin enantiomers. Journal of chromatography. A 2011, 1218 (26), 4045-51.
32.Coe, R. A.; Rathe, J. O.; Lee, J. W., Supercritical fluid chromatography–tandem mass spectrometry for fast bioanalysis of R/S-warfarin in human plasma. Journal of pharmaceutical and biomedical analysis 2006, 42 (5), 573-580.
33.Ghambari, H.; Hadjmohammadi, M., Low-density solvent-based dispersive liquid-liquid microextraction followed by high performance liquid chromatography for determination of warfarin in human plasma. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2012, 899, 66-71.
34.Ranjbar Bandforuzi, S.; Hadjmohammadi, M. R., Solvent bar microextraction using a reverse micelle containing extraction phase for the determination of warfarin from human plasma by high-performance liquid chromatography. Journal of chromatography. A 2017, 1496, 1-8.
35.Naidong, W.; Ring, P. R.; Midtlien, C.; Jiang, X., Development and validation of a sensitive and robust LC-tandem MS method for the analysis of warfarin enantiomers in human plasma. Journal of pharmaceutical and biomedical analysis 2001, 25 (2), 219-26.
36.Hou, J.; Zheng, J.; Shamsi, S. A., Separation and determination of warfarin enantiomers in human plasma using a novel polymeric surfactant for micellar electrokinetic chromatography-mass spectrometry. Journal of chromatography. A 2007, 1159 (1-2), 208-16.
37.Jensen, B. P.; Chin, P. K.; Begg, E. J., Quantification of total and free concentrations of R- and S-warfarin in human plasma by ultrafiltration and LC-MS/MS. Analytical and bioanalytical chemistry 2011, 401 (7), 2187-93.
38.Nowak, P.; Garnysz, M.; Wozniakiewicz, M.; Koscielniak, P., Fast separation of warfarin and 7-hydroxywarfarin enantiomers by cyclodextrin-assisted capillary electrophoresis. Journal of separation science 2014, 37 (18), 2625-31.
39.Nowak, P. M.; Woźniakiewicz, M.; Kościelniak, P., Cyclodextrin-assisted enantioseparation of warfarin and 10-hydroxywarfarin by capillary electrophoresis studied from the analytical and thermodynamic points of view. Journal of pharmaceutical and biomedical analysis 2016, 126, 60-65.
40.Peyrovi, M.; Hadjmohammadi, M., Synthesis of molecularly imprinted polypyrrole as an adsorbent for solid-phase extraction of warfarin from human plasma and urine. Biomedical chromatography : BMC 2015, 29 (11), 1623-8.
41.Ghoneim, M. M.; Tawfik, A., Assay of anti-coagulant drug warfarin sodium in pharmaceutical formulation and human biological fluids by square-wave adsorptive cathodic stripping voltammetry. Analytica Chimica Acta 2004, 511 (1), 63-69.
42.Sun, S.; Wang, M.; Su, L.; Li, J.; Li, H.; Gu, D., Study on warfarin plasma concentration and its correlation with international normalized ratio. Journal of pharmaceutical and biomedical analysis 2006, 42 (2), 218-22.
43.Hadjmohammadi, M.; Ghambari, H., Three-phase hollow fiber liquid phase microextraction of warfarin from human plasma and its determination by high-performance liquid chromatography. Journal of pharmaceutical and biomedical analysis 2012, 61, 44-9.
44.Ju, W.; Peng, K.; Yang, S.; Sun, H.; Sampson, M.; Wang, M. Z., A chiral HPLC-MS/MS method for simultaneous quantification of warfarin enantiomers and its major hydroxylation metabolites of CYP2C9 and CYP3A4 in human plasma. Austin journal of analytical and pharmaceutical chemistry 2014, 1 (2).
45.Peyrovi, M.; Hadjmohammadi, M., Supramolecular solvent-based microextraction of warfarin from biological samples and its determination using HPLC. Journal of the Iranian Chemical Society 2015, 12 (7), 1253-1259.
46.Fanali, S., Enantioselective determination by capillary electrophoresis with cyclodextrins as chiral selectors. Journal of Chromatography A 2000, 875 (1), 89-122.
47.Juvancz, Z.; Kendrovics, R. B.; Iványi, R.; Szente, L., The role of cyclodextrins in chiral capillary electrophoresis. Electrophoresis 2008, 29 (8), 1701-1712.
48.Luong, J. H.; Nguyen, A., Achiral selectivity in cyclodextrin-modified capillary electrophoresis. Journal of Chromatography A 1997, 792 (1), 431-444.
49.Fanali, S., Controlling enantioselectivity in chiral capillary electrophoresis with inclusion–complexation. Journal of Chromatography A 1997, 792 (1), 227-267.
50.Szejtli, J., Dimethyl-β-cyclodextrin as parenteral drug carrier. Journal of inclusion phenomena 1983, 1 (2), 135-150.
51.Guo, M.; Zhang, S.; Song, F.; Wang, D.; Liu, Z.; Liu, S., Studies on the non‐covalent complexes between oleanolic acid and cyclodextrins using electrospray ionization tandem mass spectrometry. Journal of mass spectrometry 2003, 38 (7), 723-731.
52.Jorgenson, J. W.; Lukacs, K. D., Zone electrophoresis in open-tubular glass capillaries. Analytical Chemistry 1981, 53 (8), 1298-1302.
53.Jorgenson, J. W.; Lukacs, K. D., High-resolution separations based on electrophoresis and electroosmosis. Journal of Chromatography A 1981, 218 (Supplement C), 209-216.
54.Lauer, H. H.; McManigill, D., Capillary zone electrophoresis of proteins in untreated fused silica tubing. Analytical Chemistry 1986, 58 (1), 166-170.
55.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.
56.Paull, B.; King, M., Quantitative capillary zone electrophoresis of inorganic anions. Electrophoresis 2003, 24 (12‐13), 1892-1934.
57.Terabe, S.; Otsuka, K.; Ando, T., Electrokinetic chromatography with micellar solution and open-tubular capillary. Analytical Chemistry 1985, 57 (4), 834-841.
58.Quirino, J. P.; Kim, J.-B.; Terabe, S., Sweeping: concentration mechanism and applications to high-sensitivity analysis in capillary electrophoresis. Journal of Chromatography A 2002, 965 (1), 357-373.
59.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.
60.Heiger, D. N., High performance capillary electrophoresis. 1992.
61.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.
62.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.
63.Zhou, L.; Luo, Z.; Wang, S.; Hui, Y.; Hu, Z.; Chen, X., In-capillary derivatization and laser-induced fluorescence detection for the analysis of organophosphorus pesticides by micellar electrokinetic chromatography. Journal of Chromatography A 2007, 1149 (2), 377-384.
64.Osbourn, D. M.; Weiss, D. J.; Lunte, C. E., On-line preconcentration methods for capillary electrophoresis. Electrophoresis 2000, 21 (14), 2768.
65.Kitagawa, F.; Otsuka, K., Recent applications of on-line sample preconcentration techniques in capillary electrophoresis. Journal of Chromatography A 2014, 1335, 43-60.
66.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.
67.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.
68.Liu, S.; Li, Q.; Chen, X.; Hu, Z., Field-amplified sample stacking in capillary electrophoresis for on-column concentration of alkaloids in Sophora flavescens Ait. ELECTROPHORESIS 2002, 23 (19), 3392-3397.
69.Morales, S.; Cela, R., Field-amplified sample stacking and nonaqueous capillary electrophoresis determination of complex mixtures of polar aromatic sulfonates. ELECTROPHORESIS 2002, 23 (3), 408-413.
70.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.
71.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.
72.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.
73.Huang, H.-Y.; Chiu, C.-W.; Sue, S.-L.; Cheng, C.-F., Analysis of food colorants by capillary electrophoresis with large-volume sample stacking. Journal of Chromatography A 2003, 995 (1–2), 29-36.
74.Quirino, J. P.; Terabe, S., Sample stacking of cationic and anionic analytes in capillary electrophoresis. Journal of Chromatography A 2000, 902 (1), 119-135.
75.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.
76.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.
77.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.
78.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.
79.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.
80.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.
81.Chang, P. L.; Chiu, T. C.; Chang, H. T., Stacking, derivatization, and separation by capillary electrophoresis of amino acids from cerebrospinal fluids. Electrophoresis 2006, 27 (10), 1922-1931.
82.Lin, E.-P.; Lin, K.-C.; Chang, C.-W.; Hsieh, M.-M., On-line sample preconcentration by sweeping and poly (ethylene oxide)-mediated stacking for simultaneous analysis of nine pairs of amino acid enantiomers in capillary electrophoresis. Talanta 2013, 114, 297-303.
83.Chiu, T.-C.; Chang, H.-T., Stacking and separation of fluorescent derivatives of amino acids by micellar electrokinetic chromatography in the presence of poly (ethylene oxide). Journal of Chromatography A 2007, 1146 (1), 118-124.
84.Bunch, D. R.; Wang, S., Applications of monolithic solid-phase extraction in chromatography-based clinical chemistry assays. Analytical and bioanalytical chemistry 2013, 405 (10), 3021-3033.
85.Zhang, L.; Liu, S.; Cui, X.; Pan, C.; Zhang, A.; Chen, F., A review of sample preparation methods for the pesticide residue analysis in foods. Central European Journal of Chemistry 2012, 10 (3), 900-925.
86.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.
87.Sarafraz-Yazdi, A.; Amiri, A., Liquid-phase microextraction. TrAC Trends in Analytical Chemistry 2010, 29 (1), 1-14.
88.Di Muccio, A.; Girolimetti, S.; Attard Barbini, D.; Pelosi, P.; Generali, T.; Vergori, L.; De Merulis, G.; Leonelli, A.; Stefanelli, P., Selective clean-up applicable to aqueous acetone extracts for the determination of carbendazim and thiabendazole in fruits and vegetables by high-performance liquid chromatography with UV detection. Journal of Chromatography A 1999, 833 (1), 61-65.
89.Psillakis, E.; Kalogerakis, N., Developments in liquid-phase microextraction. TrAC Trends in Analytical Chemistry 2003, 22 (9), 565-574.
90.Żwir-Ferenc, A.; Biziuk, M., Solid Phase Extraction Technique--Trends, Opportunities and Applications. Polish Journal of Environmental Studies 2006, 15 (5).
91.Ufer, M.; Kammerer, B.; Kirchheiner, J.; Rane, A.; Svensson, J.-O., Determination of phenprocoumon, warfarin and their monohydroxylated metabolites in human plasma and urine by liquid chromatography–mass spectrometry after solid-phase extraction. Journal of Chromatography B 2004, 809 (2), 217-226.
92.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.
93.Vas, G.; Vekey, K., Solid‐phase microextraction: a powerful sample preparation tool prior to mass spectrometric analysis. Journal of mass spectrometry 2004, 39 (3), 233-254.
94.Kataoka, H.; Lord, H. L.; Pawliszyn, J., Applications of solid-phase microextraction in food analysis. Journal of chromatography A 2000, 880 (1), 35-62.
95.Han, D.; Tang, B.; Ri Lee, Y.; Ho Row, K., Application of ionic liquid in liquid phase microextraction technology. Journal of separation science 2012, 35 (21), 2949-2961.
96.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.
97.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.
98.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.
99.Zang, X.-H.; Wu, Q.-H.; Zhang, M.-Y.; Xi, G.-H.; Wang, Z., Developments of Dispersive Liquid-Liquid Microextraction Technique. Chinese Journal of Analytical Chemistry 2009, 37 (2), 161-168.
100.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.
101.Herrera-Herrera, A. V.; Hernández-Borges, J.; Borges-Miquel, T. M.; Rodríguez-Delgado, M. Á., Dispersive liquid–liquid microextraction combined with nonaqueous capillary electrophoresis for the determination of fluoroquinolone antibiotics in waters. ELECTROPHORESIS 2010, 31 (20), 3457-3465.
102.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.
103.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.
104.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.
105.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.
106.Tuzen, M.; Pekiner, O. Z., Ultrasound-assisted ionic liquid dispersive liquid–liquid microextraction combined with graphite furnace atomic absorption spectrometric for selenium speciation in foods and beverages. Food chemistry 2015, 188, 619-624.
107.Zhao, Z.; Yang, X.; Zhao, X.; Bai, B.; Yao, C.; Liu, N.; Wang, J.; Zhou, C., Vortex-assisted dispersive liquid-liquid microextraction for the analysis of major Aspergillus and Penicillium mycotoxins in rice wine by liquid chromatography-tandem mass spectrometry. Food Control 2017, 73, 862-868.
108.Wang, C. C.; Chiou, S. S.; Wu, S. M., Determination of mercaptopurine and its four metabolites by large‐volume sample stacking with polarity switching in capillary electrophoresis. Electrophoresis 2005, 26 (13), 2637-2642.
109.Scopes, R. K., Protein purification: principles and practice. Springer Science & Business Media: 2013.
110.Takahashi, H.; Kashima, T.; Kimura, S.; Muramoto, N.; Nakahata, H.; Kubo, S.; Shimoyama, Y.; Kajiwara, M.; Echizen, H., Determination of unbound warfarin enantiomers in human plasma and 7-hydroxywarfarin in human urine by chiral stationary-phase liquid chromatography with ultraviolet or fluorescence and on-line circular dichroism detection. Journal of Chromatography B: Biomedical Sciences and Applications 1997, 701 (1), 71-80.
111.VanOrman, B. B.; Liversidge, G. G.; McIntire, G. L.; Olefirowicz, T. M.; Ewing, A. G., Effects of buffer composition on electroosmotic flow in capillary electrophoresis. Journal of Microcolumn Separations 1990, 2 (4), 176-180.
112.Nowak, P.; Olechowska, P.; Mitoraj, M.; Woźniakiewicz, M.; Kościelniak, P., Determination of acid dissociation constants of warfarin and hydroxywarfarins by capillary electrophoresis. Journal of pharmaceutical and biomedical analysis 2015, 112 (Supplement C), 89-97.
113.Weinberger, R., Practical capillary electrophoresis. Academic Press: 2000.
114.Ali, I.; Gupta, V. K.; Aboul‐Enein, H. Y., Chiral resolution of some environmental pollutants by capillary electrophoresis. Electrophoresis 2003, 24 (9), 1360-1374.
115.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.
116.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.
117.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.
118.Wei, G.; Li, Y.; Wang, X., Application of dispersive liquid–liquid microextraction combined with high‐performance liquid chromatography for the determination of methomyl in natural waters. Journal of separation science 2007, 30 (18), 3262-3267.
119.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.
120.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.
121.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.
122.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.
123.Thermo Scientific., Solvent Properties Chromatography Columns and Consumables.
124.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.
125.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.
126.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.
127.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), 2442-2447.
128.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.
129.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.
130.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.
131.Tseng, W. L.; Hsu, C. Y.; Wu, T. H.; Huang, S. W.; Hsieh, M. M., Highly sensitive detection of chiral amino acids by CE based on on‐line stacking techniques. Electrophoresis 2009, 30 (14), 2558-2564.
132.Bharadwaj, R.; Santiago, J. G., Dynamics of field-amplified sample stacking. Journal of Fluid Mechanics 2005, 543, 57-92.
133.Bessonova, E. A.; Kartsova, L. A.; Shmukov, A. U., Electrophoretic determination of albumin in urine using on-line concentration techniques. Journal of Chromatography A 2007, 1150 (1), 332-338.
134.Thompson, J. W.; Kaiser, T. J.; Jorgenson, J. W., Viscosity measurements of methanol–water and acetonitrile–water mixtures at pressures up to 3500bar using a novel capillary time-of-flight viscometer. Journal of Chromatography A 2006, 1134 (1), 201-209.
135.Food; Administration, D., Guidance for industry on bioanalytical method validation. Federal Register 2001, 66 (100), 28526.