- 學位論文
Ⅰ.利用毛細管電泳法對支氣管擴張劑藥物 theophylline和dyphylline之同時分析研究 Ⅱ.電場加強樣品堆積之毛細管電泳法對血漿中zotepine及norzotepine之分析研究
1.Simultaneous determination of theophylline and dyphylline by micellar electrokinetic chromatography and application in drug formulations 2.Determination of zotepine and its metabolite norzotepine in human plasma by field-amplified sample stacking and capillary electrophoresis
摘要
本論文的主題是分別利用毛細管電泳中微胞電動層析法（Micellar Electrokinetic Chromatography；MEKC）以及電場加強樣品堆積之毛細管電泳法（Field-amplified sample stacking；FASS）分別針對不同的藥物發展簡單且高感度的分析方法。主要的研究包括支氣管擴張劑的製劑分析，以及針對人體血漿中抗精神藥物zotepine以及其代謝物norzotepine的應用與分析。主要的成果摘錄如下： 1、 毛細管電泳法對支氣管擴張劑dyphylline、theophylline和caffeine之同時分析研究 本研究為利用微胞電動層析法（Micellar Electrokinetic Chromatography；MEKC），針對支氣管擴張劑theophylline 和dyphylline（dihydroxypropyl theophylline），建立一個簡單、同時並具有選擇性之定量分析法。此分析方法條件為：10 mM硼酸鹽緩衝溶液（pH 9.0）、40 mM sodium dodecyl sulfate（SDS）為陰離子界面活性劑。以caffeine作為內部標準品，theophylline 和dyphylline的線性範圍在0.03-1 mmol/mL，而二者之檢出極限分別是0.01和0.02 mmol/mL (S/N=3，壓力取樣3 sec)。影響分離的因素包括：硼酸鹽緩衝溶液的pH值和濃度以及SDS的濃度均加以探討。此分析方法可應用於dyphylline與theophylline市售錠劑之含量分析。 2、電場加強樣品堆積之毛細管電泳法對血漿中zotepine及norzotepine之分析研究 本研究為利用電場加強樣品堆積之毛細管電泳（Field-amplified sample stacking；FASS），針對人體血漿中抗精神病藥物zotepine及norzotepine，建立一個簡單、同時並具有選擇性之定量分析法。此方法分析條件為：20 mM 硼酸鹽緩衝溶液（pH 8.0）內含50 % ethylene glycol及5：1 methanol（v/v），使用固相萃取法（solid-phase extraction）來處理血漿檢品。以clozapine作為內部標準品，二待測物檢量線範圍為3.0-100.0 ng/mL，而二者之檢出極限：zotepine為1 ng/mL（相當於3.0 nM，s/n=3，電壓取樣20 sec）；norzotepine為2 ng/mL（相當於6.3 nM，s/n=3，電壓取樣20 sec）。影響分離的因素包括：硼酸鹽緩衝溶液的pH值和濃度、ethylene glycol的濃度、organic modifier添加之體積量以及檢品溶媒的組成均加以探討。此分析方法可應用於血漿中zotepine及norzotepine之含量分析。
並列摘要
The purpose of this work is directed to the development of accurate and sensitive methods for the methylxanthines by micellar electrokinetic chromatography and the analysis of zotepine and norzotepine in plasma coupling with field amplified sample stacking. The results are summarized as follow: 1.Simultaneous determination of theophylline and dyphylline by micellar electrokinetic chromatography and application in drug formulations A simple micellar electrokinetic chromatography is described for well resolution of theophylline, dyphylline and caffeine. The separation was performed at 25℃ using a background electrolyte consisting of 10 mM borate buffer at pH 9 and 40 mM sodium dodecyl sulfate (SDS) as running buffer. Under this condition, good separation with high efficiency and short analyses time required is achieved. Several parameters affecting the separation of the drugs were studied, including the pH and concentrations of the borate buffer and sodium dodecyl sulfate. Using caffeine as an internal standard (I.S.), the linear range of the method for the determination of theophylline and dyphylline was over 0.03-1 mM, the detection limit (S/N= 3; injection 0.3 psi, 3 s) was 0.01 and 0.02 mM, respectively. 2.Determination of zotepine and its metabolite norzotepine in human plasma by field-amplified sample stacking and capillary electrophoresis A field-amplified sample stacking and capillary electrophoresis is described for the determination of zotepine and its metabolite norzotepine in human plasma. The separation was performed at 25℃ using a background electrolyte consisting of borate buffer (20 mM, pH 8) containing 50 % ethylene glycol and methanol (5:1, v/v). Using clozapine as an internal standard (I.S.), the linear range of the method for the determination of zotepine and norzotepine was over 3.0-100.0 ng/mL (r≧0.999), the detection limit was 1 ng/mL (S/N=3, electric-driven injection 20 s) and 2 ng/mL (S/N=5, electric-driven injection 20 s), respectively. Application of the method to the determination of zotepine and norzotepine in human plasma proved to be feasible.