( 您好!臺灣時間:2021/07/26 10:09
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::


研究生(外文):Yueh-Chan Lee
論文名稱(外文):Determination of anti-inflammatory drugs using thermosensitive microvesicle-cloud point microextraction
指導教授(外文):Pai-Shan Chen
口試委員(外文):Shang-Da HuangHuei-Wen Chen
外文關鍵詞:cloud-point extractionthin-film hydrationbinary mixing systemPL121PF68cryo-TEM
  • 被引用被引用:0
  • 點閱點閱:48
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
方法最佳化的實驗在去離子水樣中進行,在最佳化的條件之下,萃取物質偵測之線性範圍介於50-8000 μg L-1之間,線性為0.9953-0.9995,偵測極限約為10-100 μg L-1,再現性的標準偏差在14.1%以下。以環境中水樣為真實檢體萃取得到之相對回收率為17.34-133.03%,其中Acetaminophen及Salicylic acid兩種較親水之藥物,其萃取效果濃縮倍率較差,相對回收率也較低。

A simple cloud-point extraction (CPE) method for the determination of 7 common used anti-inflammatory drugs in the natural water system was developed. The CPE system was built up on a binary mixing system of the non-ionic surfactants of Pluronic series, and the CPE kit, which was coated with PL121 and PF68 surfactants on the bottom of eppendorf, was produced vast amount efficiently by combining the thing-film hydration method which is widely used in manufacturing the clinical drug delivery system. The prepared CPE kit makes the extraction procedure in a much simpler way. Anti-inflammatory drugs (acetaminophen, salicylic acid, ketoprofen, diclofenac, indomethacin, ibuprofen, and mefenamic acid) were extracted from water specimens by adding 2 mL specimen into the CPE kit, then sonication in a water bath was performed for accelerating the thin-film hydration process. After the CPE procedure, anti-inflammatory drugs were present in the surfactant-rich phase, and were analyzed by the Ultra-performance liquid chromatography coupled to photodiode array detection (UPLC-PDA) system directly. For developing an extraction method which is friendly to the environment and non-toxic to the technician, the CPE procedure used only surfactants that were biocompatible and biodegradable, and non of organic solvent has been used.
The optimum analytical conditions for binary mixing and the CPE system were established. Under these conditions, linear calibration curves were obtained over the range of 50 to 8000 μg L-1, and exhibited coefficients of determination (R2) ranging from 0.9953 to 0.9995, with detection limits of 10 to 100 μg L-1 of each analytes. Relative standard deviations (RSDs) were from 3.2 to 12.7% for intraday (n= 5), while for inter-day (n= 15) the values were between 2.5% and 14.1%. The average relative recoveries ranged from 17.34% for acetaminophen to 133.03% for mefenamic acid
Additionally, the self-assembly trend was studied by cryo-TEM, and the optimum aggregation temperature that may produce the maximum stability of the vesicular aggregate of the binary mixing system has been correlated with the CPE experimental results. These results may study forward in CPE techniques and the drug delivery systems in the future.

誌謝 i
中文摘要 iii
Chapter 1 Introduction 1
1.1 Microscale pollutants around our environment 1
1.2 Motivation 1
1.3 Cloud-point extraction 3
1.4 Drug delivery techniques 6
1.5 Thin-film hydration 7
Chapter 2 Experimental 9
2.1 Chemicals and reagents 9
2.2 Instrumentation 10
2.3 Sample preparation 11
2.4 CPE kit preparation (thin-film hydration) 11
2.5 Preparation of binary mixing systems 11
2.6 CPE procedures 12
2.7 Size measurements 12
2.8 TEM method 13
2.9 Cryo-TEM method 13
Chapter 3 Results and discussion 14
3.1 PL121 concentration 14
3.2 Binary mixing systems 15
3.3 Optimization of PF68 ratio 17
3.4 Optimization of cloud-point extraction 17
3.4.1 Sonication time 17
3.4.2 Sonication temperature 18
3.4.3 Effect of pH on CPE 20
3.4.4 Effect of sodium chloride concentration 20
3.5 Optimization of CPE 21
3.6 Vesicle size measurments 22
3.7 Regular TEM imaging 22
3.8 Cryo-TEM imaging 23
3.9 Calibration and method validation 26
3.10 Environmental sample analysis 27
3.11 Method comparison 28
Chapter 4 Conclusions 29
Chapter 5 References 88

[1]A. Jelić, M. Gros, M. Petrović, A. Ginebreda, and D. Barceló, "Occurrence and Elimination of Pharmaceuticals During Conventional Wastewater Treatment," Emerging and Priority Pollutants in Rivers, The Handbook of Environmental Chemistry H. Guasch, A. Ginebreda and A. Geiszinger, eds., pp. 1-23: Springer Berlin Heidelberg, 2012.
[2]A. Tauxe-Wuersch, L. F. De Alencastro, D. Grandjean, and J. Tarradellas, “Occurrence of several acidic drugs in sewage treatment plants in Switzerland and risk assessment,” Water Res, vol. 39, no. 9, pp. 1761-72, May, 2005.
[3]D. Bendz, N. A. Paxeus, T. R. Ginn, and F. J. Loge, “Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Hoje River in Sweden,” J Hazard Mater, vol. 122, no. 3, pp. 195-204, Jul 15, 2005.
[4]I. Rodriguez, J. Carpinteiro, J. B. Quintana, A. M. Carro, R. A. Lorenzo, and R. Cela, “Solid-phase microextraction with on-fiber derivatization for the analysis of anti-inflammatory drugs in water samples,” J Chromatogr A, vol. 1024, no. 1-2, pp. 1-8, Jan 23, 2004.
[5]C. D. Metcalfe, X. S. Miao, B. G. Koenig, and J. Struger, “Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada,” Environ Toxicol Chem, vol. 22, no. 12, pp. 2881-9, Dec, 2003.
[6]M. Gros, M. Petrović, and D. Barceló, “Development of a multi-residue analytical methodology based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) for screening and trace level determination of pharmaceuticals in surface and wastewaters,” Talanta, vol. 70, no. 4, pp. 678-690, Nov 15, 2006.
[7]K. Kimura, H. Hara, and Y. Watanabe, “Elimination of Selected Acidic Pharmaceuticals from Municipal Wastewater by an Activated Sludge System and Membrane Bioreactors,” environ sci technol, vol. 41, no. 10, pp. 3708-3714, May 1, 2007.
[8]B. Soulet, A. Tauxe, and J. Tarradellas, “Analysis of Acidic Drugs in Swiss Wastewaters,” Int. J. Environ. Anal. Chem., vol. 82, no. 10, pp. 659-667, Jan 1, 2002.
[9]P. Lucci, D. Pacetti, N. G. Frega, and O. Núñez, Current Trends in Sample Treatment Techniques for Environmental and Food Analysis, 2012.
[10]M. Rezaee, Y. Assadi, M.-R. Milani Hosseini, E. Aghaee, F. Ahmadi, and S. Berijani, “Determination of organic compounds in water using dispersive liquid–liquid microextraction,” J. Chromatogr. A, vol. 1116, no. 1–2, pp. 1-9, May 26, 2006.
[11]M. C. Hennion, “Solid-phase extraction: method development, sorbents, and coupling with liquid chromatography,” J Chromatogr A, vol. 856, no. 1-2, pp. 3-54, Sep 24, 1999.
[12]V. Lemos, and U. Vieira, “Single-drop microextraction for the determination of manganese in seafood and water samples,” Microchim Acta, vol. 180, no. 5-6, pp. 501-507, Apr 1, 2013.
[13]H. Faraji, A. Feizbakhsh, and M. Helalizadeh, “Modified dispersive liquid-liquid microextraction for pre-concentration of benzene, toluene, ethylbenzene and xylenes prior to their determination by GC,” Microchim Acta, vol. 180, no. 11-12, pp. 1141-1148, Aug 1, 2013.
[14]M. A. Jeannot, and F. F. Cantwell, “Solvent Microextraction into a Single Drop,” Anal. Chem., vol. 68, no. 13, pp. 2236-2240, Jul 1, 1996.
[15]F. Ahmadi, Y. Assadi, S. M. Hosseini, and M. Rezaee, “Determination of organophosphorus pesticides in water samples by single drop microextraction and gas chromatography-flame photometric detector,” J Chromatogr A, vol. 1101, no. 1-2, pp. 307-12, Jan 6, 2006.
[16]Y. Li, P. S. Chen, and S. D. Huang, “Water with low concentration of surfactant in dispersed solvent-assisted emulsion dispersive liquid-liquid microextraction for the determination of organochlorine pesticides in aqueous samples,” J Chromatogr A, vol. 1300, pp. 51-7, Jul 26, 2013.
[17]W. Liu, K. Bi, X. Liu, J. Zhao, and X. Chen, “Cloud-Point Extraction Combined with LC–MS for Analysis of Memantine in Rat Plasma,” Chromatographia, vol. 69, no. 9-10, pp. 837-842, May 1, 2009.
[18]E. K. Paleologos, D. L. Giokas, and M. I. Karayannis, “Micelle-mediated separation and cloud-point extraction,” Trends. Anal. Chem., vol. 24, no. 5, pp. 426-436, May, 2005.
[19]A. S. Yazdi, “Surfactant-based extraction methods,” Trends. Anal. Chem., vol. 30, no. 6, pp. 918-929, Jun, 2011.
[20]H. Watanabe, T. Saitoh, T. Kamidate, and K. Haraguchi, “Distribution of metal chelates between aqueous and surfactant phases separated from a micellar solution of a nonionic surfactant,” Microchim. Acta, vol. 106, no. 1-2, pp. 83-90, Jan 1, 1992.
[21]H. Watanabe, and H. Tanaka, “A non-ionic surfactant as a new solvent for liquid-liquid extraction of zinc(II) with 1-(2-pyridylazo)-2-naphthol,” Talanta, vol. 25, no. 10, pp. 585-9, Oct, 1978.
[22]M. Ghaedi, A. Shokrollahi, F. Ahmadi, H. R. Rajabi, and M. Soylak, “Cloud point extraction for the determination of copper, nickel and cobalt ions in environmental samples by flame atomic absorption spectrometry,” J Hazard Mater, vol. 150, no. 3, pp. 533-40, Feb 11, 2008.
[23]J. F. Liu, R. Liu, Y. G. Yin, and G. B. Jiang, “Triton X-114 based cloud point extraction: a thermoreversible approach for separation/concentration and dispersion of nanomaterials in the aqueous phase,” Chem Commun (Camb), no. 12, pp. 1514-6, Mar 28, 2009.
[24]A. Niazi, T. Momeni-Isfahani, and Z. Ahmari, “Spectrophotometric determination of mercury in water samples after cloud point extraction using nonionic surfactant Triton X-114,” J Hazard Mater, vol. 165, no. 1-3, pp. 1200-3, Jun 15, 2009.
[25]R. Carabias-Martinez, E. Rodriguez-Gonzalo, B. Moreno-Cordero, J. L. Perez-Pavon, C. Garcia-Pinto, and E. Fernandez Laespada, “Surfactant cloud point extraction and preconcentration of organic compounds prior to chromatography and capillary electrophoresis,” J Chromatogr A, vol. 902, no. 1, pp. 251-65, Dec 1, 2000.
[26]M. Moradi, and Y. Yamini, “Surfactant roles in modern sample preparation techniques: a review,” J Sep Sci, vol. 35, no. 18, pp. 2319-40, Sep, 2012.
[27]A. S. Yazdi, “Surfactant-based extraction methods,” Trends Anal. Chem., vol. 30, no. 6, pp. 918-929, Jun, 2011.
[28]F. J. Lopez-Jimenez, S. Rubio, and D. Perez-Bendito, “Single-drop coacervative microextraction of organic compounds prior to liquid chromatography. Theoretical and practical considerations,” J Chromatogr A, vol. 1195, no. 1-2, pp. 25-33, Jun 27, 2008.
[29]M. Moradi, and Y. Yamini, “Application of vesicular coacervate phase for microextraction based on solidification of floating drop,” J Chromatogr A, vol. 1229, pp. 30-7, Mar 16, 2012.
[30]J. Dua, A. Rana, and A. Bhandari, “Liposome: methods of preparation and applications,” Int J Pharm Stud Res, vol. 3, pp. 14-20, 2012.
[31]I. U. Khan, C. A. Serra, N. Anton, and T. Vandamme, “Microfluidics: A focus on improved cancer targeted drug delivery systems,” J. Controlled Release, vol. 172, no. 3, pp. 1065-1074, Dec 28, 2013.
[32]I. Cabrera, E. Elizondo, O. Esteban, J. L. Corchero, M. Melgarejo, D. Pulido, A. Cordoba, E. Moreno, U. Unzueta, E. Vazquez, I. Abasolo, S. Schwartz, Jr., A. Villaverde, F. Albericio, M. Royo, M. F. Garcia-Parajo, N. Ventosa, and J. Veciana, “Multifunctional nanovesicle-bioactive conjugates prepared by a one-step scalable method using CO2-expanded solvents,” Nano Lett, vol. 13, no. 8, pp. 3766-74, Aug 14, 2013.
[33]S. C. d. A. Lopes, C. d. S. Giuberti, T. G. R. Rocha, D. d. S. Ferreira, E. A. Leite, and M. C. Oliveira, Liposomes as Carriers of Anticancer Drugs, 2013.
[34]D. J. Pochan, L. Pakstis, B. Ozbas, A. P. Nowak, and T. J. Deming, “SANS and Cryo-TEM study of self-assembled diblock copolypeptide hydrogels with rich nano-through microscale morphology,” Macromolecules, vol. 35, no. 14, pp. 5358-5360, Apr 24, 2002.
[35]H. Cui, T. K. Hodgdon, E. W. Kaler, L. Abezgauz, D. Danino, M. Lubovsky, Y. Talmon, and D. J. Pochan, “Elucidating the assembled structure of amphiphiles in solution via cryogenic transmission electron microscopy,” Soft Matter, vol. 3, no. 8, pp. 945-955, Jun 28, 2007.
[37]A. Sharma, and U. S. Sharma, “Liposomes in drug delivery: Progress and limitations,” int. j. pharm., vol. 154, no. 2, pp. 123-140, Aug 26, 1997.
[38]V. Singh, P. Khullar, P. N. Dave, and N. Kaur, “Micelles, mixed micelles, and applications of polyoxypropylene (PPO)-polyoxyethylene (PEO)-polyoxypropylene (PPO) triblock polymers,” Int. J. Indus. Chem., vol. 4, no. 1, pp. 1-18, 2013.
[39]K. T. Oh, T. K. Bronich, and A. V. Kabanov, “Micellar formulations for drug delivery based on mixtures of hydrophobic and hydrophilic Pluronic block copolymers,” J Control Release, vol. 94, no. 2-3, pp. 411-22, Feb 10, 2004.
[40]M. Alauddin, T. Parvin, and T. Begum, “Effect of organic additives on the cloud point of triton X-100 micelles,” J. Applied Sci., vol. 9, no. 12, pp. 2301-2306, 2009.
[41]D. A. Balazs, and W. Godbey, “Liposomes for use in gene delivery,” Journal of drug delivery, vol. 2011, pp. 1-12, Oct, 2010.
[42]D. L. Giokas, V. A. Sakkas, T. A. Albanis, and D. A. Lampropoulou, “Determination of UV-filter residues in bathing waters by liquid chromatography UV-diode array and gas chromatography-mass spectrometry after micelle mediated extraction-solvent back extraction,” J Chromatogr A, vol. 1077, no. 1, pp. 19-27, Jun 3, 2005.
[43]I. Casero, D. Sicilia, S. Rubio, and D. Pérez-Bendito, “An Acid-Induced Phase Cloud Point Separation Approach Using Anionic Surfactants for the Extraction and Preconcentration of Organic Compounds,” Analytical Chemistry, vol. 71, no. 20, pp. 4519-4526, Oct 1, 1999.
[44]T. Wang, X. Gao, J. Tong, and L. Chen, “Determination of formaldehyde in beer based on cloud point extraction using 2,4-dinitrophenylhydrazine as derivative reagent,” Food Chemistry, vol. 131, no. 4, pp. 1577-1582, Apr 15, 2012.
[45]K. Schillén, K. Bryskhe, and Y. S. Mel''Nikova, “Vesicles formed from a poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) triblock copolymer in dilute aqueous solution,” Macromolecules, vol. 32, no. 20, pp. 6885-6888, May, 1999.
[46]M. R. Payán, M. Á. B. López, R. F. Torres, M. V. Navarro, and M. C. Mochón, “Electromembrane extraction (EME) and HPLC determination of non-steroidal anti-inflammatory drugs (NSAIDs) in wastewater samples,” Talanta, vol. 85, no. 1, pp. 394-399, 7/15/, 2011.
[47]A. Macia, F. Borrull, M. Calull, and C. Aguilar, “Different sample stacking strategies to analyse some nonsteroidal anti-inflammatory drugs by micellar electrokinetic capillary chromatography in mineral waters,” J Chromatogr A, vol. 1117, no. 2, pp. 234-45, Jun 9, 2006.
[48]M. Cruz-Vera, R. Lucena, S. Cárdenas, and M. Valcárcel, “One-step in-syringe ionic liquid-based dispersive liquid–liquid microextraction,” J. Chromatogr. A, vol. 1216, no. 37, pp. 6459-6465, Sep 11, 2009.
[49]J. Wu, and H. K. Lee, “Orthogonal array designs for the optimization of liquid–liquid–liquid microextraction of nonsteroidal anti-inflammatory drugs combined with high-performance liquid chromatography-ultraviolet detection,” J. Chromatogr. A, vol. 1092, no. 2, pp. 182-190, Oct 28, 2005.
[50]X. Wen, C. Tu, and H. K. Lee, “Two-Step Liquid−Liquid−Liquid Microextraction of Nonsteroidal Antiinflammatory Drugs in Wastewater,” Anal. Chem., vol. 76, no. 1, pp. 228-232, Jan 1, 2004.
[51]M. Cruz-Vera, R. Lucena, S. Cárdenas, and M. Valcárcel, “Ionic liquid-based dynamic liquid-phase microextraction: Application to the determination of anti-inflammatory drugs in urine samples,” J. Chromatogr. A, vol. 1202, no. 1, pp. 1-7, Aug 15, 2008.
[52]T. Hirai, S. Matsumoto, and I. Kishi, “Simultaneous analysis of several non-steroidal anti-inflammatory drugs in human urine by high-performance liquid chromatography with normal solid-phase extraction,” J. Chromatogr. B, vol. 692, no. 2, pp. 375-388, May 9, 1997.
[53]H. Filik, I. Sener, S. D. Cekic, E. Kilic, and R. Apak, “Spectrophotometric determination of paracetamol in urine with tetrahydroxycalix[4]arene as a coupling reagent and preconcentration with triton X-114 using cloud point extraction,” Chem Pharm Bull (Tokyo), vol. 54, no. 6, pp. 891-6, Jun, 2006.

第一頁 上一頁 下一頁 最後一頁 top