電場加大樣品堆積之毛細管電泳法對人體血漿中Aripiprazole及其活性代謝物dehydroaripiprazole之同時分析研究

Simultaneous determination of aripiprazole and dehydroaripiprazole in human plasma by field-amplified sample stacking and capillary electrophoresis

黃佩莉(Pei-Li Huang)

指導教授 ： 陳素惠

高雄醫學大學/藥學院/藥學研究所/碩士(2009年)

摘要

本論文的研究主題是利用電場加大樣品堆積(Field-amplified sample stacking ; FASS)之毛細管電泳法對人體血漿中抗精神病藥物aripiprazole以及其代謝物 dehydroaripiprazole，建立一個簡單、同時具有選擇性之定量分析法。分離之背景電解質(background electrolyte; BGE)為: 150mM 磷酸鈉鹽緩衝溶液, pH 3.5內含40% methanol 及0.02% polyvinyl alcohol (PVA)，使用液相液相萃取法 (liquid-liquid extraction )來處理血漿檢品。並以amlodipine作為內部標準品。對影響分離的因素: 磷酸鈉鹽緩衝溶液的pH值和濃度、methanol比例、PVA濃度、檢品溶媒的組成均加以探討。此分析方法可應用於病人血漿中aripiprazole 及活性代謝物 dehydroaripiprazole之同時含
量分析。

關鍵字

毛細管電泳 ； 電場加大樣品堆積 ； 精神病

並列摘要

A sensitive high performance capillary zone electrophoresis (CZE) combining on-column field-amplified sample stacking (FASS) has been developed for simultaneous determination of aripiprazole and its active metabolite, dehydroaripiprazole, in human plasma. A sample pretreatment by means of liquid-liquid extraction (diethylether) with subsequent quantitation by FASS-CZE was used. The separation of aripiprazole and dehydroaripiprazole was performed using a background electrolyte containing 150 mM phosphate buffer (pH 3.5) with 40% methanol and 0.02% polyvinyl alcohol (PVA) as a dynamic coating to reduce analytes’ interaction with the capillary wall. The samples were injected electrokinetically (10 kV, 30s) to introduce sample cations and the applied voltage was 20 kV and on-column detection at 214 nm. Several parameters affecting the separation and sensitivity of the drug and its metabolite were studied, including reconstitution solvent, organic modifier, pH and concentration of phosphate buffer. The linear ranges of the method for the simultaneous determination of the test drugs, in plasma using amlodipine as an internal standard (IS), were over the range 5-100 ng/mL for aripiprazole and dehydroaripiprazole. The application of the proposed method for determination of aripiprazole and dehydroaripiprazole in plasma collected after oral administration of 30 mg aripiprazole (Abilify??, Otsuka) daily in one schizophrenic patient was demonstrated.

並列關鍵字

Capillary electrophoresis ； Field-amplified sample stacking ； schizophrenia

參考文獻

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