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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 郭錦樺 | |
dc.contributor.author | Hsiang-Yin Liu | en |
dc.contributor.author | 劉祥音 | zh_TW |
dc.date.accessioned | 2021-06-07T18:17:15Z | - |
dc.date.copyright | 2012-03-02 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-02-10 | |
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H., Risperidone in schizophrenia: is there a role for therapeutic drug monitoring? Ther. Drug Monit. 2011, 33, (3), 275-283. 23. Nazirizadeh, Y.; Vogel, F.; Bader, W.; Haen, E.; Pfuhlmann, B.; Grunder, G.; Paulzen, M.; Schwarz, M.; Zernig, G.; Hiemke, C., Serum concentrations of paliperidone versus risperidone and clinical effects. Eur. J. Clin. Pharmacol. 2010, 66, (8), 797-803. 24. Aymard, N.; Viala, A.; Clement, M. N.; Jacquot, M.; Vacheron, M. N.; Gauillard, J.; Caroli, F., Long-term pharmacoclinical follow-up in schizophrenic patients treated with risperidone - plasma and red blood cell concentrations of risperidone and its 9-hydroxymetabolite and their relationship to whole blood serotonin and tryptophan, plasma homovanillic acid, 5-hydroxyindoleacetic acid, dihydroxyphenylethylene- glycol and clinical evaluations. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2002, 26, (5), 975-988. 25. Levine, M.; Lovecchio, F.; Tafoya, P.; Graham, R., Paliperidone overdose with delayed onset of toxicity. Ann. Emerg. Med. 2011, 58, (1), 80-82. 26. Jones, T.; Van Breda, K.; Charles, B.; Dean, A. J.; McDermott, B. M.; Norris, R., Determination of risperidone and 9-hydroxyrisperidone using HPLC, in plasma of children and adolescents with emotional and behavioural disorders. Biomed. Chromatogr. 2009, 23, (9), 929-934. 27. Avenoso, A.; Facciola, G.; Salemi, M.; Spina, E., Determination of risperidone and its major metabolite 9-hydroxyrisperidone in human plasma by reversed-phase liquid chromatography with ultraviolet detection. J. Chromatogr. B 2000, 746, (2), 173-181. 28. Shen, Y. L.; Wu, H. L.; Ko, W. K.; Wu, S. M., Simultaneous determination of clozapine, clozapine N-oxide, N-desmethylclozapine, risperidone, and 9-hydroxyrisperidone in plasma by high performance liquid chromatography with ultraviolet detection. Anal. Chim. Acta 2002, 460, (2), 201-208. 29. Llerena, A.; Berecz, R.; Dorado, P.; de la Garza, C. S.; Norberto, M. J.; Caceres, M.; Gutierrez, J. R., Determination of risperidone and 9-hydroxyrisperidone in human plasma by liquid chromatography: application to the evaluation of CYP2D6 drug interactions. J. Chromatogr. B 2003, 783, (1), 213-219. 30. Titier, K.; Deridet, E.; Cardone, E.; Abouelfath, A.; Moore, N., Simplified high-performance liquid chromatographic method for determination of risperidone and 9-hydroxyrisperidone in plasma after overdose. J. Chromatogr. B 2002, 772, (2), 373-378. 31. Raggi, M. A.; Bugamelli, F.; Sabbioni, C.; Saracino, M. A.; Petio, C., HPLC-DAD determination of plasma levels of the antipsychotic risperidone and its main metabolite for toxicological purposes. J. Sep. Sci. 2005, 28, (3), 245-250. 32. Locatelli, I.; Mrhar, A.; Grabnar, I., Simultaneous determination of risperidone and 9-hydroxyrisperidone enantiomers in human blood plasma by liquid chromatography with electrochemical detection. J. Pharm. Biomed. Anal. 2009, 50, (5), 905-910. 33. Lemoing, J. P.; Edouard, S.; Levron, J. C., Determination of risperidone and 9-hydroxyrisperidone in human plasma by high-performance liquid- chromatography with electrochemical detection. J. Chromatogr. B 1993, 614, (2), 333-339. 34. Zhang, L.; Jiao, Z.; Yao, Z. Q.; Zhong, Y.; Zhong, M. K.; Yu, Y. Q., The validation of an LC-MS method for the determination of risperidone and its active metabolite 9-hydroxyrisperidone in human plasma. Chromatographia 2005, 61, (5-6), 245-251. 35. Cabovska, B.; Cox, S. L.; Vinks, A. A., Determination of risperidone and enantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS. J. Chromatogr. B 2007, 852, (1-2), 497-504. 36. De Meulder, M.; Remmerie, B. M. M.; de Vries, R.; Sips, L. L. A.; Boom, S.; Hooijschuur, E. W. J.; van de Merbel, N. C.; Timmerman, P. M. M. B. L., Validated LC-MS/MS methods for the determination of risperidone and the enantiomers of 9-hydroxyrisperidone in human plasma and urine. J. Chromatogr. B 2008, 870, (1), 8-16. 37. Bhatt, J.; Subbaiah, G.; Singh, S., Liquid chromatography/tandem mass spectrometry method for simultaneous determination of risperidone and its active metabolite 9-hydroxyrisperidone in human plasma. Rapid Commun. Mass Spectrom. 2006, 20, (14), 2109-2114. 38. Flarakos, J.; Luo, W.; Aman, M.; Svinarov, D.; Gerber, N.; Vouros, P., Quantification of risperidone and 9-hydroxyrisperidone in plasma and saliva from adult and pediatric patients by liquid chromatography-mass spectrometry. J. Chromatogr. A 2004, 1026, (1-2), 175-183. 39. Remmerie, B. M. M.; Sips, L. L. A.; de Vries, R.; de Jong, J.; Schothuis, A. M.; Hooijschuur, E. W. J.; van de Merbel, N. C., Validated method for the determination of risperidone and 9-hydroxyrisperidone in human plasma by liquid chromatography-tandem mass spectrometry. J. Chromatogr. B 2003, 783, (2), 461-472. 40. Aravagiri, M.; Marder, S. R., Simultaneous determination of risperidone and 9-hydroxyrisperidone in plasma by liquid chromatography/electrospray tandem mass spectrometry. J. Mass Spectrom. 2000, 35, (6), 718-724. 41. Danel, C.; Barthelemy, C.; Azarzar, D.; Robert, H.; Bonte, J. P.; Odou, P.; Vaccher, C., Analytical and semipreparative enantioseparation of 9-hydroxyrisperidone, the main metabolite of risperidone, using high-performance liquid chromatography and capillary electrophoresis validation and determination of enantiomeric purity. J Chromatogr A 2007, 1163, (1-2), 228-236. 42. Danel, C.; Chaminade, P.; Odou, P.; Bartelemy, C.; Azarzar, D.; Bonte, J. P.; Vaccher, C., Enantioselective analysis of the antipsychotic 9-hydroxyrisperidone, main metabolite of risperidone, by chiral capillary EKC using dual CDs. Electrophoresis 2007, 28, (15), 2683-2692. 43. Pucci, V.; Raggi, M.; Kenndler, E., Separation of eleven central nervous system drugs by capillary zone electrophoresis. J. Chromatogr. B 1999, 728, (2), 263-271. 44. Pucci, V.; Raggi, M. A.; Kenndler, E., Quality control of pharmaceutical formulations of neuroleptic drugs by capillary zone electrophoresis. J. Liq. Chromatogr. Relat. Technol. 2000, 23, (1), 25-34. 45. Johns, K. F.; Breadmore, M. C.; Brudo, R.; Haddad, P. R., Evaluation of Peakmaster for computer aided multivariate optimisation of a CE separation of 17 antipsychotic drugs using minimal experimental data. Electrophoresis 2009, 30, (5), 839-847. 46. Tsai, I. L.; Sun, S. W.; Liao, H. W.; Lin, S. C.; Kuo, C. H., Rapid analysis of melamine in infant formula by sweeping-micellar electrokinetic chromatography. J. Chromatogr. A 2009, 1216, (47), 8296-8303. 47. Torres, P.; Sepulveda, M. J.; Von Plessing, C., Pharmacokinetic study of risperidone. application of a HPLC method with solid phase extraction. J. Chil. Chem. Soc. 2011, 56, (1), 606-609. 48. Kuhn R., H.-K. S., Capillary electrophoresis: principles and practice. 1993. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16489 | - |
dc.description.abstract | 美國食品藥物管理局(US Food and Drug Administration)於2007 年核准paliperidone 做為精神病患急性發作及長期治療之藥物,目前已廣泛被用於精神病患者的治療。Paliperidone 的生體可用率低,藥物吸收易受高脂食物影響。其療效區間範圍狹窄,可能因個體差異而使體內paliperidone 落在療效區間之外,使治療效果不彰或發生副作用,故本研究開發並確效一靈敏的毛細管電泳膠束電動層析
法來分析人體血漿中paliperidone 藥物濃度。本研究利用Oasis® HLB 1 mL (30 mg)Extraction Cartridge 開發固相萃取法進行樣品前處理,並最佳化各項會影響膠束電動層析效力之參數。經固相萃取後樣品回溶的基質組成為10%甲醇及250 mM 磷酸,背景溶液之組成為100 mM 十二烷基硫酸鈉、75 mM 磷酸、12%乙腈及15%四氫呋喃,並使用risperidone 做為內標準品,paliperidone 可在17 分鐘內和血中內生性物質達基線分離。分析物之遷移時間一日內再現性與異日內再現性小於3.09%RSD (n=3),分析物和內標準品risperidone 的峰面積比值一日內再現性與異日內再現性小於6.03% RSD (n=3)。Paliperidone 校正曲線的線性範圍介於20 ng mL-1到200ng mL-1 之間,涵蓋臨床有效治療濃度範圍,最低偵測濃度為10 ng mL-1,準確度介在93.4%-97.9%之間。研究者針對paliperidone 開發一靈敏的毛細管電泳分析方法除了可檢測病患者血中藥物濃度,或可預測因服用paliperidone 引發外錐體副作用的可能性。本分析方法為第一個應用毛細管電泳分析平臺分析定量人體血中paliperidone 藥物濃度之分析方法,未來有潛力被應用在臨床療劑監測以維護病患用藥安全、預測治療成效以提升治療成功率。 | zh_TW |
dc.description.abstract | Determination of paliperidone in human plasma by capillary electrophoresis. A simple, accurate and sensitive method is described for the determination of paliperidone in human plasma using risperidone as the internal standard. Paliperidone was extracted from human plasma by Oasis HLB solid phase extraction (SPE) cartridge. The optimized separation is performed in a background electrolyte composed of phosphoric acid (75 mM) containing sodium dodecyl sulfate (100 mM), acetonitrile (12%, v/v), and tetrahydrofuran (15%, v/v). The peaks were detected using a UV detector set at 240 nm, and the total time for one run was about 17 min. Results showed that this analytical method was able to detect paliperidone at concentration of 10 ng/mL (S/N > 3) and the linear range was 20–200 ng mL-1, with the correlation coefficients above 0.99. Method precision and accuracy were tested at 20, 120 and 200 ng mL-1.
Intra- and interday precision of peak area ratio were less than 6.03%; method accuracy was between 93.4% and 97.9%. This is the first analytical method to quantify the concentration of paliperidone in human plasma by capillary electrophoresis. This newly developed method appears to be applicable to therapeutic drug monitoring and clinical research. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T18:17:15Z (GMT). No. of bitstreams: 1 ntu-101-R98423033-1.pdf: 1869010 bytes, checksum: 417285a088dc6babea73870529814886 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 中文摘要 ....................................................................................................................... I
英文摘要 ......................................................................................................................II 內文目錄 .................................................................................................................... III 內文目錄 壹、序論 ...................................................................................................................... 1 1.1 毛細管電泳 ..................................................................................................... 1 1.2 毛細管電泳原理簡述 ................................................................................... 1 1.3 線上濃縮技術原理 ....................................................................................... 3 1.4. Paliperidone 的基本介紹 ............................................................................. 6 貳、研究目的 ............................................................................................................ 11 參、實驗部分 ............................................................................................................ 11 3.1 儀器 .............................................................................................................. 11 3.2 藥品與試劑 ................................................................................................... 12 3.3 標準品溶液的製備 ................................................................................... 13 3.4 空白血漿製備 ............................................................................................. 13 3.5 檢體溶液製備 ............................................................................................. 13 3.6 分析HLB 管柱萃取樣品之毛細管電泳系統 ............................................. 14 3.7 分析MCX 管柱萃取樣品之毛細管電泳系統 ............................................ 15 3.8 毛細管之處理 ............................................................................................. 15 3.9 分析方法確效 ............................................................................................... 16 肆、結果與討論 ........................................................................................................ 18 4.1 內標準品的選用 ........................................................................................... 18 IV 4.2 樣品前處理條件之開發 ............................................................................... 19 4.3 分析方法開發 ............................................................................................... 22 4.4 掃集條件最佳化 ........................................................................................... 25 4.5 分析方法的確效 ........................................................................................... 27 伍、結論 .................................................................................................................... 30 參考文獻 .................................................................................................................... 31 附圖 ............................................................................................................................ 38 Figure 1. Proposed mechanism of high-salt stacking. ......................................... 38 Figure 2. Sweeping in a reduced electric field. ................................................... 39 Figure 3. Structure of paliperidone. ................................................................... 40 Figure 4. Structure of risperidone. ..................................................................... 40 Figure 5. Structure of ketanserine. ..................................................................... 41 Figure 6. The influence of sample cleanup procedures on the peak shape of risperidone and paliperidone. ............................................................................. 42 Figure 7. Electropherograms of human plasma spiked with risperidone and paliperidone use different elution solution to elute analytes from MCX solid phase extraction cartridge. ........................................................................................... 43 Figure 8. Electropherogram of spiked plasma underwent solid phase extraction with reversed washing steps. ............................................................................. 44 Figure 9. Electropherogram of 1 μg mL-1 risperidone and paliperidone standard solution. ............................................................................................................ 45 Figure 10. The influence of acetonitrile content in BGE on the separation of human plasma. .............................................................................................................. 46 V Figure 11. The influence of tetrahydrofuran content in BGE on the separation of human plasma. .................................................................................................. 47 Figure 12. The influence of phosphoric acid content in background solution on the separation of human plasma. ............................................................................. 48 Figure 13. The influence of injection time on the peak shape and intensity of human plasma. .................................................................................................. 49 Figure 14. Effect of phosphoric acid content in sample matrix on intensity of paliperidone. ...................................................................................................... 50 Figure 15. Effect of methanol percentage in sample matrix on peak area and intensity of paliperidone. ................................................................................... 51 Figure 16. Electropherogram of human plasma (A) spiked with 200 ng mL-1 risperidone and 20 ng mL-1 paliperidone and (B) blank. ................................... 52 Figure 17. Electropherogram of human plasma post-piked with risperidone, paliperidone, and 11 possible combined drugs. .................................................. 53 Figure 18. Electropherogram of human plasma (A) spiked with 200 ng mL-1 risperidone and paliperidone and (B) blank. ....................................................... 54 附表 ............................................................................................................................ 55 Analytical precision and accuracy of paliperidone in human plasma. ................. 55 Bioanalytical methods for the analysis of risperidone and paliperidone. ............. 56 | |
dc.language.iso | zh-TW | |
dc.title | 開發毛細管電泳方法分析人體血漿中Paliperidone藥物濃度 | zh_TW |
dc.title | Determination of Paliperidone in Human Plasma by Capillary Electrophoresis. | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 吳信隆,黃志清 | |
dc.subject.keyword | Paliperidone,毛細管電泳,膠束電動層析法,療劑監測,血漿, | zh_TW |
dc.subject.keyword | Paliperidone,Capillary electrophoresis,Sweeping-MEKC,Plasma,Therapeutic drug monitoring, | en |
dc.relation.page | 56 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2012-02-10 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥學研究所 | zh_TW |
顯示於系所單位: | 藥學系 |
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