以環糊精修飾微胞電動層析技術之毛細管電泳法同時分析clopidogrel及主要代謝物

Quantitative determination of clopidogrel and its main metabolite by cyclodextrin-mediated micellar electrokinetic chromatography

曾品瑄(Pin-Syuan Zeng)

指導教授 ： 陳素惠

高雄醫學大學/藥學院/藥學系碩士班/碩士(2015年)

摘要

抗凝血用藥Clopidogrel (Plavix®)為一種在臨床上廣泛使用的血小板抑制劑與抗血栓用藥，其用途可避免血管栓塞，降低中風、心肌梗塞、周邊動脈血管疾病的發生率。為達到有效治療療效，確認藥物本身的含量均一度是否達到標準是有必要的。在藥物代謝的過程中，經由肝臟代謝後大部分的含量會形成羧酸代謝物，可藉由定量此羧酸代謝物作為病人服藥依順性的指標。
利用環糊精修飾毛細管微胞電動層析法搭配紫外光偵測器，針對clopidogrel及羧酸代謝物進行分析，以建立定量藥品及血液檢體中含量的分析技術。本實驗方法係在熔矽之毛細管內充滿磷酸鹽緩衝溶液(10 mM, pH 2.5)內含50mM十二烷基硫酸鈉 (Sodium dodecyl sulfate)、15 mM (2-hydroxypropyl)-β-cyclodextrin條件下在7分鐘內完成分離，於0.2-10 μg/mL的濃度範圍內有良好的線性關係，分析物clopidogrel與clopidogrel carboxylic acid 的偵測極限皆是50 ng/mL。此簡單、快速的毛細管電泳分析技術，可成功達到線上樣品濃縮並實際應用在clopidogrel市售膜衣錠脂含量均一度以及其羧酸代謝物在血液檢體中的含量。

關鍵字

抗凝血用藥 ； 環糊精修飾微胞電動層析技術

並列摘要

Clopidogrel (Plavix®) is a potent anti-platelet and anti-thrombotic drug. It is indicated for reduction of thrombotic events including myocardial infarction, ischemic stroke and vascular death. To meet therapeutic requirement, the uniformity of content is needed. In metabolic pathway, clopidogrel undergoes rapid hydrolysis into carboxylic acid metabolite. Therefore, determination of clopidogrel carboxylic acid metabolite in plasma can be as useful tool for indicating patients’ compliance.
A simple and sensitive cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) with UV detection (200 nm) was developed and validated for the simultaneous determination of the clopidogrel and its major metabolite, carboxylic metabolite. In the optimized condition, separation of the analytes was achieved less than 7 minutes under the background electrolyte of 10 mM phosphate (pH 2.5) containing 50 mM sodium dodecyl sulfate (SDS) and 15mM (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD). The linear range of the proposed method for determination of clopidogrel and clopidogrel carboxylic acid was between 0.2-10 μg/mL. The limits of detection and quantification were 50 and 100 ng/mL for clopidogrel and its carboxylic metabolite, respectively. A simple, rapid CE-UV method using CD-MEKC was successfully established for effective analysis of clopidogrel in tablet and its carboxylic metabolite in plasma.

並列關鍵字

Clopidogrel ； Anti-platelet drug ； Cyclodextrin-mediated micellar electrokinetic chromatography

參考文獻

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