以毛細管電泳-紫外光間接偵測法對抗癲癇藥物gabapentin與vigabatrin進行定量分析

Abstract

本研究是利用毛細管電泳方法，對市售的gabapentin膠囊和vigabatrin錠劑作定量分析。Gabapentin與vigabatrin是新的抗癲癇藥物，其紫外光吸收度很低，若不經衍生化，而直接以紫外光偵測器測之，結果的靈敏度很差，故在此研究中，使用紫外光間接偵測法作為偵測方法。 在分析方法的開發中，針對可能影響分離結果的參數做一連串的探討，包括顯色劑的選擇、背景電解質的濃度和pH值及施加的電壓。經過多次的試驗後，得到一個最適化條件為5 mM的m-hydroxybenzoic acid背景電解質，以氫氧化鈉溶液調pH值至11.0，所施加的電壓為30 kV，γ-aminobutyric acid為內標準品。在此條件下，gabapentin和vigabatrin可在6分鐘內被分離出來。 以上述條件對gabapentin和vigabatrin進行分析，分別可得遷移時間的重複性和再現性之相對標準偏差為0.93 %，2.00 %及0.79 %，2.18 %；峰高度比的重複性和再現性之相對標準偏差為4.71 % ，5.08 % 及 4.78 %，5.52 %；回收率分別為101.75 % 及100.90 %；線性範圍分別為20-100 μg/mL及10-50 μg/mL；檢測極限分別為5 μg/mL及3 μg/mL。本研究所發展的分析方法可快速簡單地用於gabapentin和vigabatrin之原料藥和劑型的定量分析。

Quantitative analyses of gabapentin capsules and vigabatrin tablets were performed in the present study by capillary electrophoresis. Gabapentin and vigabatrin are new antiepilieptic drugs (AEDs) and absorbance of them are very low. Poor sensitivity was obtained by using direct UV detection without derivatization. Because of that, indirect UV detection was used in this study. During the process of method development, we investigated the influence of possible parameters on resolution, including selection of visualization agents, concentration and pH value of background electrolyte, and applied voltage. The optimal condition was found to be 5 mM m-hydroxybenzoic acid as visualization agent, which was adjusted to pH 11.0 with sodium hydroxide, 30 KV and γ-aminobutyric acid used as internal standard for quantification. Gabapentin and vigabatrin can be separated well in six minutes. For gabapentin and vigabatrin, repeatability and reproducibility of migration time (RSD) were 0.93 %, 2.00 % and 0.79 %, 2.18 %, respectively; repeatability and reproducibility of peak height ratio (RSD) were 4.71 %, 5.08 % and 4.78 %, 5.52 %, respectively. Recovery were 101.75 % and 100.90 %, respectively. The linear range of gabapentin and vigabatrin were 20-100 μg/mL and 10-50 μg/mL, respectively. The limit of detection were found to be 5 μg/mL and 3 μg/mL, respectively. The method can be used to assay raw materials and formulation products of gabapentin and vigabatrin in a fast and simple way.