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研究生:陳聖文
研究生(外文):Sheng-Wen Chen
論文名稱:利用毛細管電泳法分析含水楊酸鹽類之防曬產品及利用高分子奈米螢光顆粒分析人體血漿中排鐵劑藥物
論文名稱(外文):Capillary electrophoresis for determination of salicylates in sunscreen products and using fluorescence polymer dots to analyze deferiprone in human plasma
指導教授:吳秀梅吳秀梅引用關係
指導教授(外文):Shou-Mei Wu
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:藥學系碩士班
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:中文
論文頁數:114
中文關鍵詞:環糊精之微胞電動毛細管電泳法水楊酸鹽類防曬劑化學計量實驗設計法高分子奈米螢光顆粒排鐵劑藥物
外文關鍵詞:CD-MEKCsalicylate-type UV filterschemometric experimental designfluorescence polymer dotsiron chelating drugdeferiprone
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本論文建立一種毛細管電泳法,測定水楊酸鹽類(salicylates)防曬劑於防曬產品中之含量,也建立一種化學感測器方法測定血漿中排鐵劑藥物。
  首先本論文以添加環糊精之微胞電動毛細管電泳法 (cyclodextrin-modified micellar electrokinetic chromatography, CD-MEKC) 來分析5種常添加於市售化妝品之水楊酸鹽類防曬劑,包含homosalate (HS)、octylsalicylate (OS)、phenyl salicylate (PS)、sodium salicylate (SS)及ethylene glycol salicylate (EGS),及一因安全性問題不再許可為防曬劑用途的methyl salicylate (MS)。研究中利用化學計量實驗設計法 (chemometric experimental design) 輔助尋找最適化條件,其中界面活性劑SDS之濃度、γ-cyclodextrin之濃度及甲醇含量,對於理想分離具有統計上之意義。經進一步探討及條件優化後,最適化之條件為20 mM NaH2PO4 (pH 3.0) 含有100 mM SDS、10 mM γ-CD與40% (v/v) methanol,此方法應用於分離6種水楊酸鹽類之防曬劑成分,可在18 min內完成分離。本法萃取添加於乳霜的水楊酸鹽類防曬劑成分,所得各待測物之偵測極限於300 nm偵測下分別HS為0.2 mg/g,OS為0.2 mg/g;在214 nm偵測下PS為0.03 mg/g,MS為0.02 mg/g,SS為0.015 mg/g,EGS為0.02 mg/g。經由方法確效後,其相對標準偏差(RSD)小於12.6%,相對標準誤差(RE)小於14.2%,並可應用於5種市售產品及1種客製化商品之水楊酸鹽類分析,結果顯示與產品標示有很高的一致性。
  另一研究中,則利用高分子奈米螢光顆粒偵測人體血漿中排鐵劑藥物,利用高分子螢光材料PFBT與表面改質材料PSMA,以再沉澱法製備高分子奈米顆粒之水分散液,根據電子顯微鏡照片,高分子奈米顆粒其平均粒徑為21.9±3.8 nm。根據金屬離子選擇性及預試驗結果,選擇二價銅離子及排鐵劑藥物deferiprone (DFP) 進行後續之研究。在標準品環境中搭配40 μg/mL二價銅離子,檢測濃度範圍界於10至100 μg/mL之DFP。在最適化條件中,高分子奈米顆粒以pH 8.5之緩衝溶液稀釋;於人體血漿樣品之萃取,選擇丙酮做為去蛋白溶媒,以真空乾燥機去除溶媒,搭配3M 氯化鈉水溶液及異丙醇做為液、液萃取溶媒,可得到較高的螢光猝滅及回復比例,後續分析方法的確效正在進行當中。


One capillary electrophoresis (CE) method was developed for determination of salicylate-type UV filters in sunscreen products. The other method was using chemical sensor to determine iron chelating drugs.
 A cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) was developed for quantitative determination of five salicylate-type UV filters in sunscreen products, including homosalate (HS), octyl salicylate (OS), phenyl salicylate (PS), sodium salicylate (SS), ethylene glycol salicylate (EGS), and one ingredient, methyl salicylate (MS). MS was banned as UV filter due to its safety concern. The chemometric experimental design was utilized in this study to optimize the conditions. Three experimental variables (surfactant concentration, cyclodextrin concentration, and methanol percentage) were significant, and were investigated by the chemometric experimental design. The optimum CE buffer was 20 mM NaHPO4, pH 3.0, 100 mM SDS, 10 mM γ-CD, and 40% methanol. The migration time was less than 18 min. The LODs (S/N = 3) were 0.2 mg/g for HS, 0.2 mg/g for OS at 300 nm detection. The LODs were 0.03 mg/g for PS, 0.02 mg/g for MS and EGS, 0.015 mg/g for SS. After validation, the RSD and RE were less than 12.6 and 14.2%, respectively. The method was applied to analyze salicylate type UV filters in five commercial products and one customized product.   
 Another research tried to use the fluorescence polymer dots to detect the chelating drug in human plasma. The fluorescence polymer material PFBT and surface modifier PSMA were used to prepare the polymer dots suspension by reprecipitation method. The average particle size was about 21.9±3.8 nm that was described in images of transmission electron microscopy (TEM). In the pre-experiment, iron chelating drug deferoxamine mesylate salt (DFO), deferiprone (DFP) and deferasirox (DFX) were tested with copper ion and ferric ion, respectively. According to the results from the pre-experiment, copper ion and DFP were selected for the further research. Analyzing the drug DFP concentration from 10 to 100 μg/mL was performed with 40 μg/mL copper ion under the standard condition. In optimal condition, polymer dots were diluted with buffer at pH 8.5. Acetone was selected as the deproteinized agent, 3M sodium chloride solution and isopropanol were chosen as liquid-liquid extraction solvent for human plasma sample. This condition could observe higher fluorescence quenching and fluorescence recovery ratio. Validation and application in human plasma were under investigation in future.


中文摘要 i
Abstract iii
目錄 v
圖目錄 viii
表目錄 xiii
縮寫表 xv
第壹章、緒論 1
第一節、建立毛細管電泳法分析水楊酸鹽類之防曬劑成分 1
第二節、利用高分子奈米螢光顆粒分析排鐵劑藥物 10
第貳章、實驗材料與設備 16
第一節、建立毛細管電泳法分析水楊酸鹽類防曬劑成分 16
一、試藥與材料 16
二、實驗儀器 17
三、試藥溶液配製 18
四、乳霜萃取步驟 20
五、毛細管電泳條件 21
第二節、利用高分子奈米螢光顆粒分析排鐵劑藥物 22
一、試藥與材料 22
二、實驗儀器 24
三、試藥溶液配製 25
四、高分子奈米螢光顆粒之合成 26
五、真實檢品萃取步驟 27
六、螢光分光光度計偵測條件 27
七、重金屬離子廢液處理 28
第參章、結果與討論 29
第一節、建立毛細管電泳法分析水楊酸鹽類防曬劑成分 29
一、CE分析技術之選擇 29
二、毛細管電泳分析條件之最適化 30
三、偵測波長之選定 41
四、乳霜萃取方法之選擇 44
五、分析方法之確效 46
第二節、利用高分子奈米螢光顆粒分析排鐵劑藥物 64
一、高分子奈米螢光顆粒合成 64
二、高分子奈米螢光顆粒與排鐵劑藥物及金屬離子之預試驗 67
三、高分子奈米螢光顆粒、deferiprone與二價銅離子之反應 75
四、高分子奈米螢光顆粒、deferiprone與二價銅離子於人體血漿之反應 81
第肆章、結論 85
參考文獻 87
人體試驗研究同意證明書 92



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