以GC-FID 檢測儲藥型吩坦尼穿皮貼片劑中乙醇之方法開發及確效   全文下載

Method Development and Validation for the GC-FID Assay of Ethanol in Reservoir-type Fentanyl Transdermal Patches

在儲藥型吩坦尼穿皮輸送系統中乙醇係作為皮膚穿透的促進劑，適當的助溶劑系統中準確的乙醇含量是一項重要的品質控管項目。本研究主要在開發及確效以氣相層析- 火焰離子化檢測器（GC-FID）檢測的方法，測定儲藥型吩坦尼穿皮貼片劑（DurogesicR）中乙醇的含量。本方法利用水及超聲波振動將樣品萃取出，並加入丙酮作為內標準品。使用極性的管柱（Supelco OVI-G43, 30 m × 0.53 mm）進行氣相層析，乙醇及其他賦形劑可成功地被分離，並依據 ICH Q2A 及Q2B 規範進行分析方法確效。所有的確效參數包括：線性範圍介於0.1 到0.9 mg/mL 之間（r2 > 0.99）；準確性（在正常操作濃度之60, 100 及140% 處所測得回收率）可達98~101%，且相對標準偏差 ? 0.75%；精密度（可重複性及中間精密度）之相對標準偏差 ? 1.21%；最低檢測濃度及最低定量濃度分別為1.99 及6.03 μg/mL；而耐變性和系統適用性測試亦經確效驗證。結果顯示，此乙醇含量檢測方法可成功地應用到吩坦尼貼片劑之品質控管上。"

With ethanol acting as a skin permeation enhancer in the reservoir-type fentanyl transdermal delivery system, accurate assay of ethanol in the adapted cosolvent system is an important quality control component. This paper describes the development and validation of an isothermal gas chromatography-flame ionization detection (GC-FID) method for the assay of ethanol in reservoir-type fentanyl patches (Durogesic). Samples were extracted with water by ultrasonic vibration using acetone as the internal standard. Using a polar column (Supelco OVI-G43, 30 m × 0.53 mm) for the gas chromatographic analysis, ethanol and excipients were well resolved. The method was fully validated according to the ICH Q2A and Q2B guidelines. The range of linearity for ethanol was demonstrated from approximately 0.1 to 0.9 mg/mL (r2 > 0.99). The accuracy (recovery tests at 60, 100, and 140% of the nominal analytical concentration of 0.5 mg/mL) was determined in the range of 98~101% with RSD ≤ 0.75%. The precision (repeatability or intermediate precision) was calculated as RSD ≤ 1.21%. The detection and quantitation limits were determined to be 1.99 and 6.03 μg/mL, respectively. Furthermore, the robustness and system suitability testing were also considered. In conclusion, a validated method for the assay of ethanol in reservoir-type fentanyl transdermal patches was successfully applied to quality control practices.