利用非水相毛細管電泳法與掃掠式微胞電動層析法分離苯二氮平類藥物

Abstract

本篇研究中以非水相毛細管電泳法及掃掠式微胞電動層析法，進行分離苯二氮平類藥物之實驗。苯二氮平類藥物在醫學臨床上是屬於抗憂鬱具鎮靜安眠療效的特效藥，為法定醫療用藥。其主要效能可放鬆肌肉、治療癲癇、使人心靈平靜及抗凝血等。為避免藥物的濫用與誤用發展快速且簡便的檢測技術來進行藥物的篩選與定量是刻不容緩的重要工作。 使用非水相電泳可改善傳統水溶液電泳對於親油性藥物無法有效分離之問題，以非水相溶劑取代水進行電泳實驗可增進疏水性藥物之分離選擇性。夲研究中，我們成功的開發出在10分鐘內分析了八種苯二氮平類藥物分析物的非水相毛細管電泳法，其分離緩衝溶液組成為甲醇-乙腈(95:5,v/v)混合溶劑，其中包含450 mM 草酸和2.5 mM 三乙胺，分析物遷移時間的RSD皆小於1.25% 。 由於傳統的毛細管電泳法樣品進樣量少且光徑過短使得毛細管電泳的偵測靈敏度一直不如其他方法，夲研究利用電動層析法掃略式線上濃縮分析九種苯二氮平類藥物，可以在不改變儀器裝置條件下，藉由調整背景緩衝溶液的離子濃度、CTAB濃度及添加有機修飾劑等方式，使得分析物的注射時間能有效地增加，降低方法偵測極限至ppb等級，其最大波峰高度放大倍率可達300倍以上。

In this study, non-aqueous capillary electrophoresis (NACE) method and on-line concentration by sweeping in micellar electrokinetic chromatography (MEKC) method were employed to analyze benzodiazepines. The benzodiazepines are used clinically as sedatives to counteract anxiety. These compounds are frequently prescribed for pharmacotherapy of epilepsy, convulsion and many psychiatric disorders. They have been prescribed as muscle relaxants, tranquilizer and anticonvulsants. Benzodiazepines can lead to sudden death if misused, and have been the subject of abuse in suicide and criminal cases. The application of CE for the analysis of pharmaceutical drugs is limited because these drugs are hydrophobic and conventional aqueous CE methods do not generate useful separation. Using completely non-aqueous separation media instead of water as the CE buffer solvent allow improved selectivity. A successful separation of eight benzodiazepines drugs was completed within 10 min in a methanol-acetonitrile (95:5) buffer containing 450mM Oxalic acid and 2.5mM Triethylamine. The RSDs of migration times were less than 1.25%. However, the small sample volume and short optical length restricted the detection limits of CE. Thus, On-line concentration by sweeping in electrokinetic chromatography method was also used to improve the detection limits of benzodiazepines. The limits of detection were reduced to ppb level by the on-line concentration method. The highest response improvement was over 300-fold.