利用離子液體增強五種典型抗精神病藥之微透析回收率

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標題:	利用離子液體增強五種典型抗精神病藥之微透析回收率 Enhanced Microdialysis Recovery of Five Typical Antipsychotic Drugs by Using Ionic Liquids
作者:	許文豪
貢獻者:	藥學系劉國盛
關鍵字:	抗精神病藥物離子液體微透析 Antipsychotics Ionic liquids Microdialysis
日期:	2014
上傳時間:	2015-10-26 20:25:30 (UTC+8)
摘要:	離子液體是在攝氏一百度下即可以呈現液態的有機鹽類，近年來因為它的一些優點被應用在很多領域中。其中離子液體可做為溶劑，對多種物質都有相當好的萃取表現。本實驗利用適當條件的咪唑鹵素離子液體，於體外微透析當中來有效提升分析物的回收率。臨床上治療精神疾病病人時，經常同時使用一種以上的抗精神病藥物（多重用藥），且其在治療效果與血中濃度關係具有監測之價值，故研究中利用適當條件之分析方法偵測微透析樣品，單一步驟同時定量五個典型抗精神病藥物之微透析樣品–Chlorpromazine、Flupromazine、Triflupromazine、Thioridazine與Promethazine。高效液相層析-紫外光偵測器於C-18 (25cm×4.6mm i.d.，5μm) 管柱下，使用移動相acetonitrile：methanol：phosphate buffer (pH 5.6)=25：40：35（v/v%），流速0.9mL/min，可於33分鐘內分離五種藥品，並使用UV 波長250nm偵測定量。微透析灌流液中添加1-butyl-3-methylimidazolium halide（[Bmim][X]）類離子液體，控制微透析變因:不同種類離子液體、離子液體濃度、灌流液pH值、不同的鹽類使用、灌流速率等參數。結果指出，不同鹵素陰離子（Cl－、Br－與I－）之[Bmim]，增強微透析回收率之效力並無明顯差異（p>0.05）。而[Bmim][I]之濃度變化會明顯影響微透析回收率，以4.4mM有最佳化結果，不同藥物有6~8倍之回收率增幅。改變pH值也會明顯改變4.4mM [Bmim][I] 對回收率之影響力，於高pH值9與10時無明顯可視之回收率，但於pH 5.6時有效提升微透析回收率達10~15倍以上。灌流速率的調控也顯著成比例的影響藥物回收率。結果顯示導入離子液體於微透析技術中，能顯著地提升分析物之回收率，以達降低偵測極限濃度等更有利的分析條件。 Ionic liquid(IL) is a class of organic salts that can remain liquid state below 100 degree, and have recently been synthesized and applied in various fields. IL appears to be an ideal solvent in many extraction experiments, and could be immiscibility with water or organic solvents by simply change the ions. Owing to these advantages, this study demonstrateas the first IL using on microdialysis for enhancing recovery of analytes. Psychiatric patients usually treated with more than one antipsychotic drugs at the same time in clinic, and these drugs are also valuable for monitoring blood concentration. Therefore, it's advantageous to use suitable condition to determinate multiple antipsychotic drug including chlorpromazine, fluphenazine, promethazine, triflupromazine and thioridazine from microdialysis sample at once. The samples were separated on HPLC-UV by using Supelco Ascentis C-18 (25cm×4.6mm i.d., 5μm) column and mobile phase of acetonitrile methanol:phosphate buffer (pH 5.6) (25:40:35 (v/v)) in 0.9mL/min flow rate. All drugs were monitored and quantified by UV 250nm. Perfusate had been contained 1-Butyl-3-methylimidazolium halide, [Bmim][X], with controlling variable factors: different kinds and concentrations of ILs, buffers, pH value and matrixes of perfusate. Results of this study show that the imidazolium ILs having iodide, bromide or chloride have no significant difference on relative recovery (p>0.05). And [Bmim][I] have a optimal concentration for the recovery enhancement with 4.4mM that can reach about 6 to 8 fold increasing. The pH Value also affects ILs in relative recovery ability significantly that 4.4mM [Bmim][I] in pH5.6 could meet 10 to 15 fold recovery increasing. The drugs recovery would be inversely propotional to the flow rates with ILs using. Results of this experiment indicate that IL could significantly increase recovery of antipsychotic drugs on microdialysisand accomplish thelower limitation of detection.
關聯:	網際網路公開：2019-12-31，學年度：102，96頁
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