Microextraction and microseparation techniques and applications

MICROEXTRACTION AND MICROSEPARATION TECHNIQUES AND APPLICATIONS WEN XIUJUAN NATIONAL UNIVERSITY OF SINGAPORE 2003 MICROEXTRACTION AND MICROSEPARATION TECHNIQUES AND APPLICATIONS BY WEN XIUJUAN A THESIS SUBMITTED FOR THE DEGREE OF MASTER OF SCIENCE DEPARTMENT OF CHEMISTRY NATIONAL UNIVERSITY OF SINGAPORE 2003 Acknowledgements I wish to express my sincere gratitude to my supervisor, Professor Lee Hian Kee for his inspiring guidance, invaluable advice and great patience throughout the duration of my study I would also like to thank Ms Frances Lim, Mr Tu Chuan Hong, Dr Zhu Lingyan and all my colleagues in the Department of Chemistry for their generous contribution of their knowledge, experience and warmest assistance I am grateful to my parents for their endless understanding, concern and support The financial assistance provided by the National University of Singapore during my candidacy is also greatly appreciated i Table of contents Acknowledgements i Table of contents ii List of Tables vi List of Figures vii Abbreviations viii Summary x Chapter Preface Introduction Traditional sample preparation techniques 2.1 Liquid-Liquid extraction 2.2 Solid-phase extraction Microextraction 3.1 Sorbent-based microextraction 11 3.2 Solvent-based microextraction 12 3.2.1 Single drop extraction 3.2.1.1 Liquid-phase microextraction or solvent microextraction 13 14 3.2.1.2 Static LPME and dynamic LPME 15 3.2.1.3 Liquid-phase Microextraction / back extraction 17 3.2.1.4 Head-space LPME 18 ii 3.2.2 Hollow fiber-protected microextraction 3.2.2.1 Liquid-liquid-liquid microextraction 20 21 3.2.2.2 Static LPME with hollow fiber and dynamic LPME with hollow fiber Objects of this work 25 26 Chapter Liquid-phase microextraction of amino alcohols with analysis by capillary electrophoresis Introduction 27 Materials and methods 28 2.1 Apparatus 28 2.2 Materials 29 2.3 Extraction of water samples 30 Results and discussion 3.1 Selection of organic solvent for impregnation of the hollow fiber 32 32 3.2 Composition of the acceptor phase and donor phase 33 3.3 Extration time 34 3.4 Quantitative analysis 35 Summary 36 Chapter Liquid-phase microextraction of anaesthetics in urine combined with liquid chromatography-mass spectrometry Introduction 37 Experimental 38 iii 2.1 Liquid-liquid-liquid microextraction 38 2.2 Instrumental analysis 40 2.2.1 High-performance liquid chromatography 40 2.2.2 LC-MS 40 2.2.2.1 HPLC 40 2.2.2.2 Electrospray ionization mass spectrometry 41 2.3 Reagents and standards 41 Results and discussion 43 3.1 The effect of organic solvent 43 3.2 Selection of acceptor phase 44 3.3 Selection of donor solution 44 3.4 Effect of extraction time 45 3.5 Effect of stirring speed 46 3.6 Extraction efficiency 47 3.7 Method validation 47 3.8 Spiked sample analysis 48 Summary Chapter 50 Two-step liquid-liquid-liquid microextraction of nonsteroidal anti-inflammatory drugs in wastewater Introduction 51 Experimental 52 2.1 Two-step liquid-liquid-liquid microextraction 52 iv 2.2 Instrumentation and chromatography 55 2.3 Reagents 56 Results and discussion 56 3.1 Basic principle of extraction 56 3.2 Donor and acceptor solutions 57 3.3 Effect of extraction time 60 3.4 Quantitative analysis 61 3.5 Real-world water sample 62 Summary 63 Chapter Conclusion 64 References 66 List of Publications 75 v List of Tables Table 1-1 Important parameters for commonly used solvents in LLE Table 1-2 Column selection in SPE Table 2-1 Efficiencies of different impregnation solvents Table 2-2 Enrichment of pindolol utilizing different donor and acceptor solutions Table 2-3 Quantitative results of LLLME-CE Table 3-1 Selection of organic solvents Table 3-2 The influence of acceptor phase on anaesthetics preconcentration Table 3-3 The influence of donor phase on anesthetic preconcentration Table 3-4 Performance of LLLME-LC-MS Table 3-5 Real sample analysis Table 4-1 Effect of compositions of donor and acceptor solutions on enrichment factor Table 4-2 Verification of recovery of the first step two-step LLLME Table 4-3 Performance of two-step LLLME vi List of Figures Figure1-1 Classification of microextraction abbreviations, refer to page viii) techniques (For explanation Figure 1-2 Expanded views of dynamic LPME within the microsyringe Figure 1-3 Schematic of liquid-liquid-liquid microextraction Figure 1-4 Schematic of the LLLME extraction device Figure 2-1 Chemical structures of amino alcohols Figure 2-2 Schematic of the LLLME device of Figure 2-3 Electropherogram of a spiked water sample (2 µg/ml) obtained by LLLME-CE Capillary: 60-cm (effective length, 47 cm) × 50-µm I D.; buffer, 30 mM Tris-H3PO4 (pH 2.5); detection, UV 195 nm; voltage, 20 kV; injection, 100 mbar·s; injection time, 0.1 Peaks: (1) 2-amino-1-phenylethanol; (2) norephedrine; (3) pindolol; (4) atenolol Figure 2-4 Plot of preconcentration factors for amino alcohols versus extraction time Injection time, min; other conditions as in Figure 2-2 Figure 3-1 Structures of Lidocaine, Bupivacaine and Dibucaine Figure 3-2 Effect of extraction time on enrichment factor Figure 3-3 Effect of stirring speed on enrichment factor Figure 3-4 LC-MS-SIM chromatogram of urine sample after extraction: (a) blank urine sample; (b) urine sample spiked with 50 ng/mL of each analyte Figure 4-1 Schematic of two-step LLLME device: (a) first-step extraction unit and (b) second-step extraction unit In (a), for clarity, only pieces of hollow fibre are shown Figure 4-2 Structures of IBP and MPA Figure 4-3 Effect of extraction time on enrichment factor Concentration, 50µg/L for MPA, 300µg/L for IBP Donor phase, 25mM HCl , acceptor phase, 0.1M NaOH Extraction stirring speed, 700 rpm Figure 4-4 Chromatogram of wastewater sample after extraction: (a) blank wastewater vii sample; (b) wastewater sample spiked with ng/mL of each analyte viii 15 30 15 30 Figure 4-4 Chromatogram of wastewater sample after extraction: (a) blank wastewater sample; (b) wastewater sample spiked with ng/mL of each analyte Summary The results of this work demonstrate the successful development and application of LLLME of NSAIDs from water samples, using ten pieces of hollow fiber for the first step, and a single piece for the second step With the obvious advantages of high enrichment factor (up to 1.50×104-fold), the two-step LLLME is capable of achieving lower detection limits (100ng/L and lower for NSAIDs) compared with other extraction techniques like LLE, SPE (200ng/L), SPME (0.1-10µg/L) and single step LPME 62 (1µg/L)[96,151] As the extraction principle is the same as single-step LLLME, the optimization of the entire process can be simplified based on just one step, the second step The procedure is convenient to operate and highly cost-effective Potential memory effects of the fibers can be overcome by using fresh hollow fibers each time Two-step LLLME has been shown to be effective for the pretreatment of domestic wastewater containing NSAIDs 63 Chapter Conclusions The research described in the foregoing chapters clearly illustrated that liquid-liquid-liquid microextraction (LLLME) can be efficiently applied to drug analysis and as alternative methods to conventional macroscale sample preparation techniques Liquid-liquid-liquid microextraction (LLLME), a new development of solvent microextraction that is based on the principle of supported liquid membrane (SLM), integrates sampling, extraction, concentration, and sample introduction into a single step and offers a solvent-free alternative to traditional methods The LLLME setup is very simple Normally, the sample vial is placed on a magnetic stirrer, which provides the agitation to facilitate the extraction The microdrop of aqueous solution (acceptor phase) was introduced into a small porous polypropylene hollow fiber by a microsyringe and held at the tip of the needle throughout the whole extraction The fiber is then dipped for s into the organic phase for impregnation of the porous wall, and then placed into the donor solution in the sample vial The syringe is fixed on the retort stand The magnetic stirrer is switched on to start the extraction After a prescribed time, the fiber (with the attached syringe) is removed from the sample solution The extract in the fiber is withdrawn into the syringe and directly analyzed In LLLME, the porous polypropylene hollow fiber with impregnated organic solvent is used as an interface between the acceptor phase and the donor phase Because of the small size of the pores, particles and unwanted large molecules in the matrix are prevented from interfering with extraction so that LLLME can be effectively used in the extraction of drugs from biological matrix With selective extraction, sample preparation is simplified and typically results in a significant savings in time and precision LLLME was demonstrated to be an effective method for sample preparation in drug 64 analysis when combined with CE and LC/MS The factors influencing extraction efficiency such as selection of organic solvent, composition of acceptor phase and donor phase, extraction time, and stirring speed were investigated and optimized Good enrichment factors, linearity and precision were obtained In a novel approach to LLLME, two-step LLLME was developed and shown to be more efficient than basic one-step LLLME Two-step LLLME was demonstrated to provide high enrichment factors, thus allowing the achievement of low detection limits for the analysis of non-steroidal anti-inflammatory drugs in domestic wastewater There is one limitation of the microextraction techniques developed in this work: the difficulty in automating the process especially in providing on-line integration with various instrumental techniques Clearly this is a challenging problem that should be a focus of any future work on these techniques Nevertheless, the procedures developed in this work have been shown to be very easy to use and give very good analytical data, and can be introduced and effectively used in virtually any analytical laboratory 65 Reference [1] R.M Smith, Newsweek, June 16, 1986, 15 [2] Ray H Liu, Daniel E Gadzala, Handbook of Drug Analysis: Applications in Forensic and Clinical Laboratories [3] J Pawliszyn, Applications of Solid Phase Microextraction.Royal Society of Chereity, London, UK, 1999 [4] D.M Baer, W.R Dito, (Eds.) Interpretations in Therapeutic Drug Monitoring, Am Soc Clin Path., Chicago, 1981 [5] A Richens, V Marks, (Eds.) Therapeutic Drug Monitoring, Churchill Livingston, London, 1995 [6] R.H Liu, A.M McKeehan, C Edwards, G.F Foster, W.D Bensley, J.G Langner, A.S Walia, J Forensic Sci., 39, (1994) 1501 [7] S.J Mule, G.A Casella, J Anal Toxicol., 12, (1988) 153 [8] C.L Hornbeck, R.J Czarny, J Anal Toxicol., 13, (1989) 144 [9] B.D Paul, L.D Jr Mell, J.M Mitchell, J Irving, A J Novak, J Anal Toxicol., 9, (1985) 222 [10] J.M Moore, Forensic Sci Rev., 2, (1990) 79 [11] P Moleman, V Dijk, J.Clin.Chem., 36, (1990) 732 [12] W.E Lambert, E Meyer, A.P.D Leenheer, J Anal Toxicol, 19, (1995) 73 [13] S.M Sottolano, J Forensic Sci., 33, (1988) 1415 [14] P Mangin, A.A Lugnier, A.J Chaumont, J Anal Toxicol., 11, (1987) 27 [15] J.B.F Lloyd, D.A Parry, J Anal Toxicol., 13, (1989) 163 [16] M Schafroth, W Thormann, D Allenmann, Electrophoresis, 15, (1994) 72 66 [17] W Thormann, P Meier, C Marcolli, F Binder, J Chromatogr., 545, (1991) 445 [18] W Thormann, S Lienhard, P Wernly, J Chromatogr., 636, (1993) 137 [19] P Wernly, W Thormann, Anal Chem., 64, (1992) 2155 [20] I.S Lurie, Am Lab., 28, (1996) 26 [21] F Tagliaro, C Poiesi, R Aiello, R Dorizzi, S Ghielmi, M Marigo, J Chromatogr., 638, (1993) 303 [22] V.C Trenerry, J Robertson, R.J Wells, J Chromatogr Sci., 32, (1994) [23] A.C Allen, D.A Cooper, J.M Moore, J Forensic Sci., 30, (1985) 908 [24] H.W Avdovicj, S.H Jin, W.L Wilson, Can Soc Forensic Sci J., 18, (1985) 24 [25] C.C Clark, Microgram, 16, (1983) 25 [26] T.C Kram, I.S Lurie, Forensic Sci Int., 55, (1992) 131 [27] M.J LeBelle, C Savard, B A Dawson, D B Black, L K Katyal, F Zrcek, A W By, Forensic Sci Int., 71, (1995) 215 [28] T Mils, III, J C Roberson, H H McCurdy, W H Wall, Instrumental Data for Drug Analysis, Elsevier: New York, Vol 5, 1991 [29] Forensic Applications of Mass Spectrometry, J Yinon, Ed., CRC Press: Boca Raton, FL, 1987 [30] Forensic Mass Spectrometry, J Yinon, Ed., CRC Press: Boca Raton, FL, 1995 [31] V.M Papa, D.W Ou, J.P Bederka, In Recent Developments in Mass Spectrometry in Biochemistry, Medicine and Environmental Research, Frigerio A Ed., Elsevier: Amsterdam, Netherlands, 1983; p87 [32] R Saferstein, In Handbook of Forensic Sciences, R Saferstein, Ed., Prentice Hall: Englewood Cliffs, NJ, 1982; p 91 67 [33] G.W Milne, H.M Fales, N Law, In Instrumental Applications in Forensic Drug Chemistry, M Klein, A V Kruegel, S.P Sobol, U S Government Printing Office: Washington, DC, 1987; p 91 [34] M Ma, F.F Cantwell, Anal Chem., 70, (1998) 3912 [35] S Pedersen-Bjergaard, K.E Rasmussen, Anal Chem., 71, (1999) 2650 [36] D.N Bailey, M.J Kelner, Anal Toxicol., 8, (1984) 26 [37] H.M Stevens, J Forensic Sci Soc., 24, (1984) 577 [38] H.M Stevens, J Forensic Sci Soc., 25, (1985) 67 [39] D Fretthold, P Jones, G Sebrosky, I Sunshine, J Anal Toxicol., 10, (1986) 10 [40] J Balkon, B.J Donnelly, Anal Toxicol., 6, (1982) 181 [41] M.A Peat, L Kopjuk, J Forensic Sci., 24, (1979) 46 [42] Alan J Handley, Extraction Methods in Organic Analysis, Boca Raton : Sheffield Academic Press; CRC Press, 1999; p 63 [43] D.D Blevins, M.P Henry, Am Lab., 27(8), (1995) 32 [44] K Ensing, J.P Franke, A Termink, X.-H Chen, R.A de Zeeuw, J Forensic Sci., 37, (1992) 460 [45] A.H.B Wu, N Liu, Y.-J Cho, K.G Johnson, S.S Wong, J Anal Toxicol., 17, (1993) 215 [46] G.L Lensmeyer, D.A Wiebe, B.A Darcey, J Chromatogr Sci., 29, (1991) 444 [47] B.K Gan, L.D Baugh, R.H Liu, A.S Walia, J Forensic Sci 36, (1991) 1331 [48] J.G Langner, B.K Gan, R.H Liu, L.D Baugh, P Chand, J.-L Weng, C Edwards, A.S Walia, Clin Chem., 37, (1991) 1595 [49] D.D Blevins, S.K Schultheis, LC-GC, 12, (1994) 12 68 [50] C Markell, D.F Hagen, V.A Bunnelle, LC-GC Int., 4, (1991) 10 [51] X.-H Chen, J Wijsbeek, J.-P Franks, R.A de Zeeuw, J Forensic Sci., 37, (1992) 61 [52] X.-H Chen, J.-P Franke, R.A de Zeeuw, Forensic Sci Rev., 4, (1992) 147 [53] The Separation Times; J&W Scientific: Folsom, CA, 1989; Vol 3, p [54] G.E Platoff, J.A Gere, Forensic Sci Rev., 3, (1991) 117 [55] R.E Majors, LC-GC, 9, (1991) 332 [56] R.E Majors, LC-GC, 4, (1986) 972 [57] P Dimson, S Brocato, R E Majors, Amer Lab., 18 (10), (1986) 86 [58] K.C Van Horne, Ed Sorbent Extraction Technology; Analytichem International: Harbor City, CA, 1985 [59] M.R Harkey, M.L Stolowitz, In Advances in Analytical Toxicology, Vol 1; Baselt, R C., Ed.; Biomedical Publications: Foster City, CA, 1984; Chapter [60] C.L Arthur, J Pawliszyn, Anal Chem., 62 (1990) 2145 [61] M Yashiki, T Miyazaki, T Kojima, Hochudoku, 12 (1994), 120 [62] M Chiaroti, R Marsili, J Microcolumn Sep., (1994) 577 [63] X.P Lee, T Kumazawa, K Sato, Int J of Legal Medicine, 107 (1995) 310 [64] R.F Mindrup, Chem N.Z 59 (1995) 21 [65] M Yashiki, N Nagasawa, T Kojima, T Miyazaki, Y Iwasaki, Jpn J Forensic Toxical., 13, (1995) 17 [66] T Kumazawa, K Watanabe, K Sato, H Seno, A Ishii, O Suzukil, Jpn J Forensic Toxicol., 13 (1995) 207 [67] M Yashiki, T Kojima, T Miyazaki, N Nagasawa, Y Iwasaki, K Hara, Forensic Sci 69 Int., 76 (1995) 169 [68] M Krogh, K Johansen, F Tonnesen, K.E Rasmussen, J Chromatogr B: Biomed Appl., 673 (1995), 299 [69] N Nagasawa, M Yashiki, Y Iwasaki, K Hara, T Kojima, Nippon Iyo Masu Supekutoru Gakkai Koenshu, 20 (1995) 127 [70] H Seno, T Kumazawa, A Ishiji, M Nishikawa, H Hattori, O Suzuki, Jpn, J Forensic Toxicol., 13 (1995) 211 [71] K Ameno, C Fuke, S Ameno, H Kinoshita, I Ijiri, J.-Can Soc Forensic Sci., 29 (1996) 43 [72] T Kumazawa, K Sato, H Seno, A Ishii, O Suzuki, Chromatographia, 43 (1996) 59 [73] H Seno, T Kumazawa, A Ishii, M Nishikawa, K Watanabe, H Hattori, O.Suzuko, Jpn J Forensic Toxicol., 14 (1996) 30 [74] N Xu, S Vandegrift, G.W Sewell, Chromatographia, 42 (1996) 313 [75] X.P Lee, T Kumazawa, K Sato, O Suzuki, Chromatographia, 42 (1996) 135 [76] B Karlberg, S Thelander, Anal Chim Acta, 98 (1978) [77] F.H Bergamin, J.X Mediiros, B.F Reis, E.A Zagatto, Anal Chim Acta, 101 (1978) [78] H Liu, P.K Dasgapta, Anal Chem., 68 (1996) 1817 [79] M.A Jeannot, F.F Cantwell, Anal Chem., 68 (1996) 2236 [80] M.A Jeannot, F.F Cantwell, Anal Chem., 69 (1997) 235 [81] W.Z Nernst, Phys Chem., 47, (1904) 52 [82] W.K Lewis, W.G Whitman, Ind Eng Chem., 16, (1924) 1215 70 [83] E.L Cussler, Diffusion: Mass Transfer in Fluid Systems; Cambridge University Press: Cambridge, 1984; Chapters 1, 2, and 11 [84] M.A Jeannot, F.F Cantwell, Anal Chem., 68 (1997) 2935 [85] Y He, H.K Lee, Anal Chem., 69 (1997) 4634 [86] Y Wang, Y.C Kwok, Y.He, H.K Lee, Anal Chem., 70 (1998) 4610 [87] L Hou, H.K Lee, J Chroma A, 976 (2002) 377 [88] M Ma, F.F Cantwell, Anal Chem., 71 (1999) 388 [89] G Shen, H.K Lee, Anal Chem., 75 (2003) 98 [90] E Psillakis, N Kalogerakis, J Chromatogr A, 907 (2001) 211 [91] S Pálmarsdóttir, B Lindegård, P Deininger, L.E Edholm, L Mathiasson, J.Å Jönsson, J Capillary Electrophor., (1995) 185 [92] S Pálmarsdóttir, L Mathiasson, J.Å Jönsson, L.E Edholm, J Chromatogr B, 688 (1997) 127 [93] S Pálmarsdóttir, E Thordarson, L.E Edholm, J.Å Jönsson, L Mathiasson, Anal Chem., 69 (1997) 1732 [94]T.G Halvorsen, S Pedersen-Bjergaard, K.E Rasmussen, J Chromatogr A, 909 (2001) 87 [95] T.G Halvorsen, S Pedersen-Bjergaard, K.E Rasmussen, J Chromatogr B, 760 (2001) 219 [96] K.E Rasmussen, S Pedersen-Bjergaard, M Krogh, H.G Ugland, T Granhaug, J Chromatogr A, 873 (2000) [97] S Pedersen-Bjergaard, K.E Rasmussen, Electrophoresis, 21 (2000) 579 [98] L.Y Zhu, L Zhu, H.K Lee, J Chromatogr A, 924 (2001) 407 71 [99] L Hou, X Wen, C Tu, H.K Lee, J Chromatogr A, 979 (2002) 163 [100] G Shen, H.K Lee, Anal Chem., 74, (2002) 648 [101] L Zhao, H.K Lee, Anal Chem., 74, (2002) 2486 [102] M.E Roche, R.P Oda, D Machacek, G.M Lawson, J.P Landers, Anal Chem., 69, (1997) 99 [103] J.P Landers, Clin Chem., 41, (1995) 495 [104] D.F Swaile, D.E Burton, A.T Balchuyas, M.J Sepanik, J Chem Sci., 26, (1988) 406 [105] K.D Altria, D.C Luscombe, J Pharm Biomed Anal., 11, (1993) 415 [106] R Weinberger, I.S Lurie, Anal Chem., 63, (1991) 823 [107] I.S Lurie In Analysis of Addictive and Misused Drugs, Adamovics, J.A Ed.: Marcel Dekker, New York, 1995: pp151 [108] A Schmutz, W Thormann, Electrophoresis, 15, (1994) 51 [109] P Lukkari, T Nyman, M.-L, Riekkola, J Chromatogr A, 674 (1994) 241 [110] J.M Cruickshank, B.N.C Prichard, in: Beta-Blockers in Clinical Practice, Churchill Livingstone, New York, 1988 [111] C.L Davies, J Chromatogr., 531 (1990) 131 [112] J.R Hampton, Eur Heart J., 17 (Suppl B) (1996) 17 [113] T Ohshima, T Takayasu, J Chromatogr B 726 (1999) 185 [114] T Watanabe, A Namera, M Yashiki, Y Iwasaki, T Kojima, J Chromatogr B, 709 (1998) 225 [115] J Drewe, S Rufer, J Huwyler, E Kusters, J Chromatogr B 691 (1997) 105 [116] S Ito, K Tsukada, J Chromatogr A, 943 (2001) 39 72 [117] S Riediker, R.H Stadler, Anal Chem., 2000 [118] M Dubois, D Fluchard, E Sior, Ph Delahaut, J Chromatogr B, 753 (2001) 189 [119] L.D Bo, P Mazzucchelli, A Marzo, J Chromatogr A, 854 (1999) [120] M Van de Wiele, K.D Wasch, J Vercammen, D Courtheyn, H De Brabander, S Impens, J Chromatogr A, 904 (2000) 203 [121] K.A Thomsson, N.G Karlsson, G.C Hansson, J Chromatogr A, 854 (1999) 131 [122] N Zhang, S.T Fountain, H Bi, D.T Rossi, Anal Chem 72, (2000) 800 [123] S Souverain, S Rudaz, D Ortelli, E Varesio, J.L Veuthey, J Chromatogr B, 784 (2003) 117 [124] M Rajanikanth, K.P Madhusudanan, R.C Gupta, J Chrimatogr B, 783 (2003) 391 [125] Z Yu, M Abdel-Rehim, D Westerlund, J Chromatogr B, 654 (1994) 221 [126] H.G Ugland, M Krogh, K.E Rasmussen, J Chromatogr B, 749 (2000) 85 [127] M Ma, F F Cantwell, Anal Chem., 1998, 70, 3912 [128] E Psillakis, N Kalogerakis, J Chromatogr A, 907 (2001) 211 [129] S Heitmeier, G Blaschke, J Chromatogr B, 721 (1999) 109 [130] T Hirai, S Matsumoto, Ikuokishi, J Chromatogr B, 692 (1997) 375 [131] W Ahrer, E Scherwerk, W Buchberger, J Chromatogr A, 910 (2001) 69 [132] S Ollers, S R Muller, J Chromatogr A, 911 (2001) 226 [133] M Farre, D Barcelo, J Chromatogr A, 938 (2001) 187 [134] G Gonzalez, R Ventura, J Chromatogr A, 719 (1996) 251 [135] L Florida, A M Pietropaolo, M Tavazzani, F.M Rubino, A Colombi, J Chromatogr B, 726 (1999) 95 73 [136] J Klimes, G Zimova, P Kastner, V Klimesova, K Palat, J Liq Chromatogr & Rel.Tech 24 (2001) 2257 [137] D Boberic-Borojevic, D Radulovic, D Ivanovic, P Ristic, J Pharm and Biomed Anal., 21(1999) 15 [138] E Nivaud-Guernet, M Guernet, D Ivanovic, M Medenica, J Liq Chromatogr , 17 (1994) 2343 [139] M Bogusz, M Erkens, R.D Maier, I Schroder, J Liq Chromatogr , 15 (1992)127 [140] L Shi, Y Ma, Z Cai, Biomed Chromatogr., 12(1998) 27 [141] O.W Reif, P Solkner, J.Rupp, J Pharm Sci & Tech., 50(1996) 399 [142] M.J Martin, F Pablos, Talanta, 49 (1999) 453 [143] C Arcelloni, J Chromatogr B, 763 (2001) 195 [144] R Gawroński, B Wrzesińska, J Memb Sci., 168 (2000) 213 [145] H.G Ugland, M Krogh, K.E Rasmussen, J Chromatogr B, 749 (2000) 85 [146] M Krogh, H Grefslie, K.E Rasmussen, J Chromatogr B, 689 (1997) 357 [147] K Johansen Reubsaet, H.R Norli, P Hemmersbach, K.E Rasmussen, J Pharm.Biomed Anal., 18 (1998) 667 [148] S Li, S.G Weber, Anal Chem., 69 (1997) 1217 [149] R Eisert, J Pawliszyn, Crit Rev Anal Chem., 27 (1997) 103 [150] M Moeder, S.Schrader, M Winkler, P Popp, J Chromatogr A, 873 (2000) 95 74 List of Publications L Hou, X Wen, C Tu, H.K Lee, Combination of liquid-phase microextraction and on-column stacking for trace analysis of amino alcohols by capillary electrophoresis J Chromatogr A 979 (2002), 163 X Wen, C Tu, H.K Lee, Two-step liquid-liquid-liquid microextraction of nonsteroidal anti-inflammatory drugs in wastewater (submitted to Anal Chem.) X Wen, S.Y Oh, H.K Lee, Liquid-phase microextraction of anaesthetics in urine combined with liquid chromatography-mass spectrometry (under preparation) 75 [...]... polydimethylsiloxane-divinylbenzene IS internal standard FIE flow injection extraction SME solvent microextraction SDE single drop extraction LPME liquid phase microextraction BSA bovine serum albumin RSD relative standard deviation viii SME/BE solvent microextraction with simultaneous back extraction HS-LPME headspace-liquid phase microextraction OSF organic solvent film LPME/HF liquid phase microextraction with hollow... extraction Headspace LPME Figure 1-1 Classification of microextraction techniques (For explanation of abbreviations, refer to page viii) 10 3.1 Sorbent-based microextraction Microextraction of drugs has, to date, found its greatest application with the technique of solid phase microextraction (SPME) and in particular fibre SPME SPME is an effective adsorption and desorption technique, which eliminates the... Key parameters like the concentration of donor and acceptor solutions and extraction times were investigated Sensitivity enhancement of >15000-fold could be achieved x Chapter 1 Preface 1 Introduction Drug analysis is growing in importance owing to the need to understand therapeutic and toxic effects of drugs and the continuing development of more selective and effective drugs [1-3] Interest in drug analysis... including efficiency, selectivity and be applicable to various compounds and matrices, but are also easy to use, inexpensive and compatible with a wide range of analytical instruments In this respect, miniaturization has became an important trend in the development of sample preparation techniques, for it offers solutions that are simpler, faster, and more environmentally and economically attractive than... concentration may be determined from absolute amount extracted Based on the extracting phase, microextraction methods currently can be classified into sorbent-based microextraction (60-75) and solvent-based microextraction (35, 79-101), as shown in Figure 1-1 9 Microextraction Methods Solvent-based microextracton Sorbent-bases microextraction SPME Fiber In-tube Single drop extraction Others Direct extraction... miniaturization, microscale sample preparation techniques are attracting more attention in analytical chemistry This work focused on one microscale sample preparation approach – liquid-liquid-liquid microextraction (LLLME), which is quick, inexpensive and uses simple equipment found in most analytical laboratories The development and applications of this microextraction procedure including investigation... SPE use a large amount of solvent, which influences trace analysis and causes environmental pollution and health concerns Initial efforts to address the problems of large solvent consumption and poor automation included the development of flow injection extraction (FIE) FIE was first described in 1978 by 12 Karlberg and Thelander [77] and by Bergamin et al [78] In conventional FIE procedures, an aqueous... scheme resulted in a 27× enrichment, a 3min extraction, and 13% relative standard deviation (RSD) while static extraction gave a 12× enrichment, 15 min extraction time and 10% RSD After extraction, the extract can be directly injected into a gas chromatograph (GC) for analysis They are shown to be fast, economical, and simple one-step microextraction techniques This work was extended for the analysis of... resonance (NMR) spectrometry and mass spectrometry (MS) are highly valued and widely used now because of their intrinsic capabilities of providing analytical results with high specificities [23-33] Modern automated chromatographic, spectrometric and mass spectroscopic instruments, as well as hyphenated methods allow analysis to be carried out more rapidly and with greater sensitivity and precision [34] Although... matrix that cannot be handled by the analytical instrument directly and to bring the analytes to a suitable concentration level for analysis Also, amenability to automation is increasingly a desirable attribute of sample preparation [35] 2 In the analysis of drugs, liquid-liquid extraction and solid-phase extraction are the most commonly used techniques for preconcentration and cleanup of samples prior .. .MICROEXTRACTION AND MICROSEPARATION TECHNIQUES AND APPLICATIONS BY WEN XIUJUAN A THESIS SUBMITTED FOR THE DEGREE OF MASTER... understand therapeutic and toxic effects of drugs and the continuing development of more selective and effective drugs [1-3] Interest in drug analysis is being focused on improving methodologies, and. .. extracting phase, microextraction methods currently can be classified into sorbent-based microextraction (60-75) and solvent-based microextraction (35, 79-101), as shown in Figure 1-1 Microextraction