以毛細電泳分離具對掌異構物之藥物的方法開發與應用

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：4

、訪客IP：3.135.217.228

姓名

李佳恬(Chia-Tien Li) 查詢紙本館藏

畢業系所

化學學系

論文名稱

以毛細電泳分離具對掌異構物之藥物的方法開發與應用
(Application of Caplillary Electrophoresis to Separate Enantiomeric Pharmaceutical Drugs)

相關論文

★ 以質譜技術探討非共價鍵結蛋白質聚合物之結構	★ 以液相層析質譜儀檢測水樣與生物檢體中全氟界面活性劑之濃度
★ 利用液相層析串聯質譜技術檢測水環境中藥物殘留物之方法開發與應用	★ 直鏈式烷基苯基二甲基銨鹽類陽離子型界面活性劑在水環境中微量檢測方法的研究
★ 芳香族磺酸鹽類有機污染物在水環境中的分析與研究	★ 以固相萃取及氣相層析質譜儀對水環境中壬基苯酚類持久性有機污染物之分析與研究
★ 以固相萃取法及氣相層析質譜儀對水環境中動情激素類有機污染物之分析與研究	★ 利用熱裂解直接高溫衍生化法快速分析直鏈式烷基三甲基銨鹽之方法建立與探討
★ 利用感應偶合電漿質譜儀檢測半導體製程用化學品中微量金屬不純物之分析研究	★ 應用毛細管電泳間接偵測方法分離四級銨鹽界面活性劑
★ 利用毛細管電泳結合線上濃縮方法分離奈磺酸鹽之機制探討	★ 快速分析水環境中醫療藥品殘留物之研究與探討
★ 以毛細管電泳法與電灑游離質譜法探討內包錯合物之研究	★ 以氣相及液相層析質譜儀分析具荷爾蒙效應物質之方法開發
★ 以離子配對高效液相層析儀檢測螢光增白劑在不同基質中之研究	★ 以氣相層析質譜儀檢測具荷爾蒙效應添加劑之方法開發與研究

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

[檢視]

[下載]

本電子論文使用權限為同意立即開放。
已達開放權限電子全文僅授權使用者為學術研究之目的，進行個人非營利性質之檢索、閱讀、列印。
請遵守中華民國著作權法之相關規定，切勿任意重製、散佈、改作、轉貼、播送，以免觸法。

摘要(中)

近年來環境檢測之發展對藥物殘留物(pharmaceutical residues)開始產生注目，大量的藥物持續地製造、消耗並排泄到環境之中，但其後環境中會發生的狀況、即將面對的命運與這些殘留物會造成的影響仍是大家未知的問題。特別是對於具對掌特性的藥物，由於不同的對掌異構物(enantiomer)對生物體的生理活性與毒性皆有所不同，目前仍無法完全了解其對環境所遭成的影響，所以此類藥物的研究已引起大眾的關心。
　　本研究將針對凱妥普洛芬(ketoprofen)與異布洛芬(ibuprofen)兩種屬於非類固醇類消炎藥(nonsteroidal anti-inflammatory drugs，簡稱NSAIDs)的對掌異構物進行分析與研究。目前這兩種藥物殘留物都被歸類為「新興污染物」(emerging contaminants)，其副作用可能對人與動物造成衝擊。
　　為檢測台灣市售的成藥與環境水樣品中是否含有凱妥普洛芬與異布洛芬對掌異構物，本研究以毛細管電泳儀(capillary electrophoresis，簡稱CE)搭配紫外光燈源進行實驗。先將成藥直接溶於甲醇(methanol)，並過濾注入毛線管電泳儀做檢測；另外再以固相萃取法(solid phase extraction，簡稱SPE) 萃取出環境水樣品中的待測物。緩衝溶液為20 mM的醋酸鈉，內含10 mM羧酸根-β-環糊精與30 mM三甲基-β-環糊精為對掌選擇劑，同時將pH調整為5.0，在此條件下可於基線完全分離兩組對掌待測物並進行定量工作。檢測結果顯示所測成藥是以消旋混合物的模式存在，並將檢測之結果與包裝上之含量進行比較後，得到之誤差率皆在15 %以下，顯示本方法具有良好的準確度。在200 mL的環境水樣品中，四個對掌待測物之定量極限(limit of quantitation，簡稱LOQ)為1.0 µg/L，水樣品中的添加標準品回收率皆在70 %以上，相對標準偏差(relative standard deviation，簡稱RSD)皆在7.5 %以下，然而，在五個所選擇的水樣品中皆未偵測到四個對掌待測物的存在。
　　此外，為增進選擇性與靈敏度，本研究另行發展一套螢光衍生化為的方法，並搭配雷射誘導螢光儀為偵檢器(laser-induced fluorescence，簡稱LIF)。不過由於螢光衍生化方法的產率不穩定與對基質效應的低容許度，故此螢光衍生化的方法並不適用於本研究。

摘要(英)

Recently, pharmaceutical residues are an emerging concern in environ- mental research. Large quantities of pharmaceuticals are continuously produced, consumed, and excreted into the environment, but the subsequent environmental occurrence, fate, and effects of these residues are not well understood, especially the work on understanding the chiral pharmaceutical residues in our environ- ment. Chirality should be concerned due to their possible different biological and/or toxicological effects from one another and from the racemate.
　Ibuprofen and ketoprofen were used as the model chiral compounds in our study, which are the widely used nonsteroidal anti-inflammatory drugs (NSAIDs) in Taiwan. These two residues have been demonstrated as emerging contami-nants which can cause side effects in organisms and has raised increasing concern about their impact on wildlife and human health.
　A method of capillary electrophoresis (CE) with UV detector was developed to determine the ibuprofen and ketoprofen enantiomers in over-the-counter (OTC) drugs sold in Taiwan and environmental water samples. For OTC drugs, the samples were directly dissolved in methanol and filtered before CE analysis. For environmental water samples, they were extracted by solid-phase extraction (SPE). The analytes were then separated and quantitated by CE with 20 mM sodium acetate buffer, consisting of 10 mM CM-β-CD and 30 mM TM-β-CD used as chiral selectors in dual cyclodextrin system, at pH 5.0. Baseline separation of two pair of chiral compounds confirmed the specificity of the method. Less than 18% of quantitation errors comparison with the contents displaying on the drug-packings and our results for selected OTC-drugs proved the accuracy of the method. The limit of quantitation (LOQ) was less than 1.0 µg/L for each enantiomer in 200 mL of environmental water sample. The spiked recoveries of four enantiomers were above 70 % while RSD was below 7.5 %. However, four enantiomers were not detected in five selected environmental water samples.
　Furthermore, a fluorescent derivatization procedure and CE-laser-induced fluorescence (LIF) detection methods were developed to enhance the sensitivity and selectivity. However, due to the unstability of the derivatives and the low tolerance to matrix effects, the preliminary results show that CE-LIF was not suitable for this kind of studies.

關鍵字(中)

★ 環糊精
★ 非類固醇類消炎藥
★ 對掌異構物
★ 毛細管電泳

關鍵字(英)

★ cyclodextrin
★ enantiomers
★ NSAIDs
★ capillary electrophoresis

論文目次

中文摘要　　　　　　　　　　　　　　　　　　　I
英文摘要　　　　　　　　　　　　　　　　　　　III
謝誌　　　　　　　　　　　　　　　　　　　　　V
目錄　　　　　　　　　　　　　　　　　　　　　VI
圖目錄　　　　　　　　　　　　　　　　　　　　IX
表目錄　　　　　　　　　　　　　　　　　　　　XI
第一章　前言　　　　　　　　　　　　　　　　 1
1-1　研究緣起　　　　　　　　　　　　　　　　1
1-2　研究目標　　　　　　　　　　　　　　　　4
第二章　文獻回顧　　　　　　　　　　　　　　6
2-1　藥物殘留物　　　　　　　　　　　　　　　6
2-1-1　藥物殘留物的來源與影響　　　　　　　　　6
2-1-2　非類固醇類消炎藥　　　　　　　　　　　　8
2-1-3　相關研究文獻　　　　　　　　　　　　　　10
2-2　毛細管電泳法　　　　　　　　　　　　　　16
2-2-1　基本原理　　　　　　　　　　　　　　　　16
2-2-2　電滲透流與帶電荷粒子的遷移行為　　　　　17
2-3　主客錯合現象　　　　　　　　　　　　　　20
2-3-1　基本概念　　　　　　　　　　　　　　　　20
2-3-2　環糊精　　　　　　　　　　　　　　　　　20
2-3-3　內包錯合物　　　　　　　　　　　　　　　23
2-4　對掌異構物的分離　　　　　　　　　　　　26
2-4-1　對掌異構物之簡介　　　　　　　　　　　　26
2-4-2　對掌異構物分離之重要性　　　　　　　　　28
2-4-3　毛細管電泳法於對掌異構物之分離與環糊精　29
2-4-4　雙環糊精系統　　　　　　　　　　　　　　31
2-5　螢光偵測法　　　　　　　　　　　　　　　34
2-5-1　雷射誘導螢光儀　　　　　　　　　　　　　34
2-5-2　螢光衍生化　　　　　　　　　　　　　　　37
2-6　固相萃取法　　　　　　　　　　　　　　　40
第三章　實驗步驟與樣品分析　　　　　　　　　 44
3-1　實驗藥品與設備　　　　　　　　　　　　　44
3-1-1　實驗藥品　　　　　　　　　　　　　　　　44
3-1-2　儀器設備　　　　　　　　　　　　　　　　46
3-2　實驗步驟　　　　　　　　　　　　　　　　48
3-2-1　標準品的配製　　　　　　　　　　　　　　48
3-2-2　緩衝溶液的製備　　　　　　　　　　　　　49
3-2-3　毛細管的處理　　　　　　　　　　　　　　49
3-2-4　毛細管電泳儀參數設定　　　　　　　　　　51
3-2-5　螢光衍生化步驟　　　　　　　　　　　　　52
3-2-6　市售成藥前處理步驟與保存　　　　　　　　53
3-2-7　固相萃取步驟　　　　　　　　　　　　　　54
3-3　水樣採集　　　　　　　　　　　　　　　　56
第四章　結果與討論　　　　　　　　　　　　　 57
4-1　紫外光燈源系統中對掌異構物之分離　　　　57
4-1-1　波長選擇　　　　　　　　　　　　　　　　57
4-1-2　對掌異構物之分離　　　　　　　　　　　　57
4-2　螢光衍生化之探討　　　　　　　　　　　　61
4-2-1　螢光衍生化反應步驟　　　　　　　　　　　61
4-2-2　反應時間對衍生化反應之影響　　　　　　　63
4-2-3　搖晃效果對衍生化反應之影響　　　　　　　65
4-2-4　螢光衍生法的穩定度與再現性　　　　　　　66
4-2-5　雷射誘導螢光系統中對掌異構物之分離　　　67
4-3　檢量線　　　　　　　　　　　　　　　　　71
4-3-1　紫外光燈源系統之檢量線　　　　　　　　　71
4-3-2　雷射誘導螢光儀系統之檢量線　　　　　　　71
4-4　市售成藥之對掌異構物成分確認　　　　　　73
4-4-1　紫外光燈源系統之成分確認　　　　　　　　73
4-4-2　雷射誘導螢光系統之成分確認　　　　　　　75
4-5　固相萃取　　　　　　　　　　　　　　　　79
4-6　真實水樣之分析結果　　　　　　　　　　　　81
第五章　結論與建議　　　　　　　　　　　　　 88
5-1　結論　　　　　　　　　　　　　　　　　　88
5-2　建議　　　　　　　　　　　　　　　　　　89
第六章　參考文獻　　　　　　　　　　　　　　 90

參考文獻

01.林宛靜，快速分析水環境中醫療藥品殘留物之研究與探討，碩士論文，國立中央大學化學研究所，民國92年。
02.金台寶，近紅外線影像技術在印刷品鑑定方面的應用，印刷科技，第22卷，第3期，21-39，民國96年。
03.陳詩欣，成藥市場成長減速，經濟日報，民國96年。
04.Abushoffa, A. M.; Fillet, M.; Hubert, P.; Crommen, J., Prediction of selectivity for enantiomeric separations of uncharged compounds by capillary electrophoresis involving dual cyclodextrin systems, J. Chromatogr. A, 2002, 948, 321-329.
05.Abushoffa, A. M.; Fillet, M.; Servais, A.; Hubert, P.; Crommen, J., Enhancement of selectivity and resolution in the enantioseparation of uncharged compounds using mixtures of oppositely charged cyclodextrins in capillary electrophoresis, Electrophoresis, 2003, 24, 343-350.
06.Ali, I.; Gupta, V. K.; Aboul-Enein, H. Y.; Chiral resolution of some environmental pollutants by capillary electrophoresis, Electrophoresis, 2003, 24, 1360-1374.
07.Baeyens, W. R. G.; Weken, G. V.; Haustraste, J.; Aboul-Enein, H. Y.; Corveleyn, S.; Remon, J. P., Garcia-Campana, A. M.; Deprez, P., Application of the restricted-access precolumn packing material alkyl-diol silica in a column-switching system for the determination of ketoprofen enantiomers in horse plasma, J. Chromatogr. A, 2000, 871, 153-161.
08.Bayle, C.; Couderc, F.; Froehlich, P.; Enhanced sensitivity using laser-induced fluorescence detection with HPLC and capillary electrophoresis, American Biotechnology Laboratory, 2003, April, 30-34.
09.Blanco, M.; Gonz?lez, J. M.; Torras, E., Enantiomeric purity determination of ketoprofen by capillary electrophoresis: evelopment and validation of the method, Anal Bioanal Chem, 2003, 375, 157-163.
10.Bonato, P. S.; Lama, M. P. F. M. D.; Carvalho, R. Enantioselective determination of ibuprofen in plasma by high-performance liquid chromatography–electrospray mass spectrometry, J. Chromatogr. B, 2003, 796, 413-420.
11.Boyd, G. R.; Reemtsma, H.; Grimm, D. A.; Mitra, S., Pharmaceuticals and personal care products (PPCPs) in surface and treated waters of Louisiana, USA and Ontario, Canada, The Science of the Total Environmental, 2003, 311, 135-149.
12.Chen, M. H., Ding, W. H., Separation and migration behavior of positional and structural naphthalenesulfonate isomers by cyclodextrin-mediated capillary electrophoresis, J. Chromatogr. A, 2004, 1033, 167-172.
13.Chen H. S.; Wang, P. L.; Ding, W. H., Using liquid chromatography-ion trap mass spectrometry to determine pharmaceutical residues in Taiwanese rivers and wastewaters, Chemosphere, 2008, 72, 863-869.
14.Cserh?ti, T.; Forg?cs, E., Effect of carboxymethyl-β-cyclodextrin on the hydrophobicity parameters of steroidal drugs, Carbohydrate Polymers, 1999, 38, 171-177.
15.Daughton, C. G., Non-regulated water contaminants: emerging research, Environmental Impact Assessment, 2004, 24, 711-732.
16.Daughton, C. G.; Ternes, T. A, Pharmaceuticals and personal care product in the environment: agents of subtle change, Environmental Health Perspectives, 1999, 107, 907- 938.
17.Dey, J.; Monhanty, A.; Roy, S.; Khatua, T., Cationic vesicles as chiral selector for enantioseparations of nonsteroidal antiinflammatory drugs by micellar electrokinetic chromatography, J. Chromatogr. A, 2004, 1048, 127-132.
18.Du, X.; Zhang, H.; Deng, Y.; Wang, H. Design and synthesis of a novel fluorescent reagent, 6-oxy-(ethylpiperazine)-9-(2’-methoxycarbonyl) fluorescein, for carboxylic acids and its application in food samples using high-performance liquid chromatography, J. Chromatogr. A, 2008, 1178, 92-100.
19.Ducret, A.; Pepin, T. P.; Lortie, R., Chiral high performance liquid chromotography resolution of ibuprofen esters, J. Pharm. Biomed. Anal., 1998, 16, 1225-1231.
20.Fanali, S.; Aturki, Z., Use of cyclodextrins in capillary electrophoresis for the chiral resolution of some 2-arylpropionic acid non-steroidal anti-inflammatory drugs, J. Chromatogr. A, 1995, 694, 297-305.
21.Farr?, M.; Ferrer, I.; Ginebreda, A.; Figueras, M.; Olivella, L., Determination of drugs in surface water and wastewater samples by liquid chromatography–mass spectrometry: methods and preliminary results including toxicity studies with Vibrio fischeri, J. Chromatogr. A, 2001, 938, 187-197.
22.Fillet, M.; Chankvetadze, B.; Crommen, J.; Blaschke, G., Designed combination of chiral selectors for adjustment of enantioseparation selectivity in capillary electrophoresis, Electrophoresis, 1999, 20, 2691-2697.
23.Fillet, M.; Hubert, P.; Crommen, J., Method development strategies for the enantioseparation of drugs by capillary electrophoresis using cyclodextrins as chiral additives, Electrophoresis, 1998, 19, 2834-2840.
24.Garrison, A. W., Probing the Enantioselectivity of CHIRAL pesticides, Environ. Sci. Technol., 2006, 40, 16-23.
25.Gibson, R.; Becerril-Bravo, E.; Silva-Castro, V.; Jim?nez, B., Determination of acidic pharmaceuticals and potential endocrine disrupting compounds in wastewaters and spring waters by selective elution and analysis by gas chromatography–mass spectrometry, J. Chromatogr. A, 2007, 1169, 31-39.
26.Gl?wka, F.; Karazniewicz, M., Enantioselective CE method for pharmacokinetic studies on ibuprofen and its chiral metabolites with reference to genetic polymorphism, Electrophoresis, 2007, 28, 2726-2737.
27.Gros, M.; Petrovic, M.; Barcel?, D.; 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, 2006, 70, 678-690.
28.Grushka, E.; Lam, S.; Chassin, J., Fluorescence labeling of dicarboxylic acids for high performance liquid chromatographic separation, Anal. Chem., 1978, 50, 1398-1399.
29.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, J. Mass Spectrom., 2003, 38, 723-731.
30.Gyllenhaal, O.; Stefansson, M., Reversal of elution order for profen acid enantiomers in normal phase LC on Chiralpak AD, J. Pharm. Biomed. Anal., 2008, 46, 860-863.
31.Ha, P. T. T.; Hoogmartens, J.; Schepdael, A. V., Recent advances in pharmaceutical applications of chiral capillary electrophoresis, J. Pharm. Biomed. Anal., 2006, 41, 1–11.
32.Harris, D. C., Quantitative chemical analysis, six edition, 2002, W. H. Freeman and Company.
33.Heo, S.; Cho, S.; Cheon, J.; Choi, M.; Im, D.; Kim, J. J.; Choi, Y. G.; Jeon, D. Y.; Chung, S.; Shim, C.; Kim, D.,Pharmacokinetics and pharmacodynamics of ketoprofen plasters, Biopharm. Drugs Dispos., 2008, 29, 37-44.
34.Huang, C. Z.; Santa, T.; Okabe, K.; Imai, K., Capillary electrophoresis with laser induced-fluorescence detection of profens derivatized with the water-soluble fluorogenic reagent 4-N-(4-N’-aminoethyl)piperazino-7- nitro-2,1,3-benzoxadiazole, J. Chromatogr. A, 2003, 1011, 193-201.
35.Jabor, V. A.; Lanchote, V. L.; Bonato, P. S., Enantioselective analysis of ibuprofen in human plasma by anionic cyclodextrin-modified electrokinetic chromatography, Electrophoresis, 2002, 23, 3041-3047.
36.Jim?nez, M. C.; Miranda, M. A.; Vay?, L., Triplet excited states as chiral reporters for the binding of drugs to transport proteins, J. Am. Chem. Soc., 2005, 127, 10134-10135.
37.Kasprzyk-Hordem, B.; Dinsdale, R. M.; Guwy, A. J., The effect of signal suppression and mobile phase composition on the simultaneous analysis of multiple classes of acidic/neutral pharmaceuticals and personal care products in surface water by solid-phase extraction and ultra performance liquid chromatography–negative electrospray tandem mass spectrometry, Talanta, 2008, 74, 1299-1312.
38.Kibler, M.; B?chmann, K., New derivatization method for carboxylic acids in aqueous solution for analysis by capillary electrophoresis and laser-induced fluorescence detection, J. Chromatogr. A, 1999, 836, 325-331.
39.Klegeris, A.; Maguire, J.; McGeer, P. L., S- but not R-enantiomers of flurbiprofen and ibuprofen reduce human microglial and THP-1 cell neurotoxicity, Journal of Neuroimmunology, 2004, 152, 73-77.
40.Kondo, J.; Suzuki, N.; Naganuma, H.; Imaoka, T.; Kawasaki, T., Nakanishi, A.; Kawahara Y., Enantiospecific Determination of Ibuprofen in Rat Plasma Using Chiral Fluorescence Derivatization Reagent, (-)-2-[4-(1- Aminoethy1)-phenyl]-6-methoxybenzoxazole, Biomed. Chromatogr., 1994, 8, 170-174.
41.Kosjek, T.; Heath, E.; Krbavcic, A., Determination of non-steroidal anti-inflammatory drug (NSAIDs) residues in water samples, Environment International, 2005, 31, 679-685.
42.Kr?gel, I.; Bodmeier, R., Development of a multifunctional matrix drug delivery system surrounded by an impermeable cylinder, Journal of Controlled Release, 1999, 61, 43-50.
43.Kubota, K.; Fukushima, T.; Yuji, R.; Miyano, H.; Hirayama, K.; Santa, T.; Imai, K., Development of an HPLC-fluorescence determination method for carboxylic acids related to the tricarboxylic acid cycle as a metabolome tool, Biomed. Chromatogr., 2005, 19, 788-795.
44.K?mmerer, K., Pharmaceuticals in the Environment, Source, Fate, Effects and Risks, 2001, Springer-Verlag, Berlin.
45.Leli?vre, F.; Gareil, P., Chiral separations of underivatized arylpropionic acids by capillary zone electrophoresis with various Cyclodextrins Acidity and inclusion constant determinations, J. Chromatogr. A, 1996, 735, 311-320.
46.Liao, W. S.; Lin, C. H.; Chen, C. Y.; Kuo, C. M.; Liu, Y. C.; Wu, J. C.; Lin, C. E., Enantioseparation of phenothiazines in CD-modified CZE using single isomer sulfated CD as a chiral selector, Electrophoresis, 2007, 28, 3922-3929.
47.Li, C.; Benet, L. Z.; Grillo, M. P., Enantioselective covalent binding of 2-phenylpropionic acid to protein in vitro in rat hepatocytes, Chem. Res. Toxicol, 2002, 15, 1480-1487.
48.Lin, B. L.; Tokai, A.; Nakanishi, J., Deviation from additivity with estrogenic mixtures containing 4-nonylphenol and 4-tert-octylphenol detected in the E-SCREEN assay, Environ. Sci. Technol., 2005, 39, 4833-4840.
49.Lin, W. C.; Chen, H. C.; Ding, W. H., Determination of pharmaceutical residues in waters by solid-phase extraction and large-volume on-line derivatization with gas chromatography–mass spectrometry, J. Chromatogr. A, 2005, 1065, 279-285.
50.Lin, X.; Zhu, C.; Hao, A., Evaluation of newly synthesized derivative of cyclodextrin for the capillary electrophoretic separation, J. Chromatogr. A, 2004, 1059, 181-189.
51.Liu, Q.; Inoue, T.; Kirchhoff, J. R.; Huang, C.; Tillekeratne, L. M. V.; Olmstead, K.; Hudson, R. A., Chiral separation of highly negatively charged enantiomers by capillary electrophoresis, J. Chromatogr. A, 2004, 1033, 349-356.
52.L?ffler, D.; Ternes, T. A., Determination of acidic pharmaceuticals, antibiotics and ivermectin in river sediment using liquid chromatography-tandem mass spectrometry, J. Chromatogr. A, 2003, 1021, 133-144.
53.Maci?, A.; Borrull, F.; Calull, M.; Aguilar, C., Different sample stacking strategies to analyse some nonsteroidal anti-inflammatory drugs by micellar electrokinetic capillary chromatography in mineral waters, J. Chromatogr. A, 2006, 1117, 234-245.
54.Magnusson, J.; Wan, H.; Blomberg, L. G., Illustration of a simple and versatile scheme for reversing enantiomeric elution order and facilitating enantiomeric impurity determination in capillary electrophoresis, Electrophoresis, 2002, 23, 3013-3019.
55.Makino, K.; Itoh, Y.; Teshima, D.; Oishi, R., Determination of nonsteroidal anti-inflammatory drugs in human specimens by capillary zone electrophoresis and micellar electrokinetic chromatography, Electrophoresis, 2004, 25, 1488-1495.
56.Ma, L.; Han, J.; Wang, H.; Gu, J.; Fu, R., Capillary electrophoresis enantioseparation of drugs using β-cyclodextrin polymer: Intramolecular synergistic effect, Electrophoresis, 1999, 20, 1900-1903.
57.Matthijs, N.; Hemelryck, S. V.; Maftouh, M.; Massart, D. L.; Heyden, Y. V., Electrophoretic separation strategy for chiral pharmaceuticals using highly-sulfated and neutral cyclodextrins based dual selector systems, Analytical Chemica Acta, 2004, 525, 247-263.
58.McWhorter, S.; Soper, S. A., Near-infrared laser-induced fluorescence detection in capillary electrophoresis, Electrophoresis, 2000, 21, 1267-1280.
59.Oliveira, A. R. M.; Cesarino, E. J.; Bonato, P. S., Solid-phase microextraction and chiral HPLC analysis of ibuprofen in urine, J. Chromatogr. B, 2005, 818, 285-291.
60.?llers, S.; Singer, H. P.; F?ssler, P.; M?ller, S. R., Simultaneous quantification of neutral and acidic pharmaceuticals and pesticides at the low-ng/ l level in surface and waste water, J. Chromatogr. A, 2001, 911, 225-234.
61.P?ze, X.; Hem?ndez, L., Biomedical Applications of Capillary Electrophoresis with Laser-Induced Fluorescence Detection, Biopharm. Drug Dispos, 2001, 22, 273–289.
62.Penn, S. G. ; He, F.; Green, M. K.; Lebrilla, C. B., The use of heated capillary dissociation and collision-induced dissociation to determine the strenghth of noncovalent bonding interactions in gas-phase peptide-cylcodextrin complexs, J. Am. Soc. Mass Spectrom, 1997, 8, 244-252.
63.Petrovića, M.; Debeljak, Ž.; Blažvić, N., Optimization of gas chromatographic method for the enantioseparation of arylpropionic non-steroidal anti-inflammatory drug methyl esters, J. Pharm. Biomed. Anal., 2005, 39, 531-534.
64.Rahavendran, S. V.; Karnes H. T., Visible diode laser-induced fluorescence detection of phenylacetic acid in plasma derivatized with nile blue and using precolumn phase transfer catalysis, Anal. Chem., 1997, 69, 3022-3027.
65.Skoog, D.A.; Holler, F.J.; Nieman, T.A., Principles of instrumental analysis, fifth edition, 1998, Thomson Learning, Inc.
66.Stumpf, M.; Ternes, T. A.; Wilken, R.; Rodrigues, S. V.; Baumann, W., Polar drug residues in sewage and natural waters in the state of Rio de Janeiro, Brazil, The Science of the Total Environment, 1999, 225, 135-141.
67.Tanaka, Y.; Kishimoto, Y.; Terabe, S., Separtion of acidic enantiomers by capillary electrophoresis-mass spectrometry employing a partial filling technique, J. Chromatogr. A, 1998, 802, 83-88.
68.Tanaka, Y.; Terabe, S., Enantiomer separation of acidic racemates by capillary electrophoresis using cationic and amphoteric β-cyclodextrins as chiral selectors, J. Chromatogr. A, 1997, 781, 151-160.
69.Vanderford, B. J.; Pearson, R. A.; Rexing, D. J.; Snyder, S. A., Analysis of endocrine disruptors, pharmaceuticals, and personal care products in water using liquid chromatography/tandem mass spectrometry, Anal. Chem., 2003, 75, 6265-6274.
70.Verleysen, K.; Sandra, P., Separation of chiral compounds by capillary electrophoresis, Electrophoresis, 1998, 19, 2798-3833.
71.Vermeulen, B.; Remon, J. P., Validation of a high-performance liquid chromatographic method for the determination of ibuprofen enantiomers in plasma of broiler chickens, J. Chromatogr. B, 2000, 781, 243-251.
72.Vollhardt, K. P. C.; Schore, N. E., Organic chemistry: structure and function, fourth edition, 2002, W. H. Freeman and Company.
73.Wang, Z.; Ouyang J.; Baeyens, W. R. G., Recent developments of enantioseparation techniques for adrenergic drugs using liquid chromatography and capillary electrophoresis: A review, J. Chromatogr. B, 2008, 862, 1-14.
74.Zerbinati, O., Trotta, F., Giovannoli, C., Baggiani, C., Giraudi, G., Vannoi A, New derivatives of cyclodextrins as chiral selectors for the capillary electrophoretic separation of dichlorprop enantiomers, J. Chromatogr. A, 1998, 810, 193-200.
75.Zhu, F.; Zhao, W.; Zhao, X.; Suo, Y.; Liu, S.; You, J., Determination of Free Fatty Acids by High Performance Liquid Chromatography with Fluorescence Detection and Identification with Mass Spectrometry, Chin J Anal Chem, 2007, 35, 489-494.
76.Zohmann, A.; Hawel, R.; Klein, G.; Kullich, W.; L?tsch, G., S(+)-ibuprofen (dexibuprofen)-excellent tolerance has not to be combined with poor clinical efficacy, Inflammopharmacology, 1998, 6, 75-79.

指導教授

丁望賢(Wang-Hsien Ding)

審核日期

2008-6-30

推文