藥品殘留溶劑檢驗方法之建立與開發研究

Establishing an Analytical Method of Residual solvents-in Pharmaceuticals by using Headspace GC-MS

藥品中殘留溶劑為藥物或賦形劑製造或使用過程中，或藥物製劑生產過程中殘存的有機揮發性物質。由於殘留溶劑無治療用途，因此應盡可能除去，以符合藥物、賦形劑和產品規格要求、GMP或其他品質標準。本計畫擬利用頂空氣相層析質譜法（Headspace gas chromatography mass spectrometry, HS-GC/MS）針對美國藥典殘留溶劑Class 1、Class 2A及Class 2B中 23種化合物，並以限量規範為偵測極限LOD，期建立一個快速定性分析方法。GC/MS分析條件如下：層析管柱使用VF-624 capillarycolumn，以升溫模式及選擇性離子監測模式（Selective Ion Monitoring, SIM）分析待測物，於18分鐘內完成Class 1、2A分析。研究結果與USP之氣相火焰離子偵測法（Gaschromatography-flame ionization detector, GC-FID）相比較，若特定殘留溶劑參照USP方法執行，未能有理想之感度，可參考本方法。

Residual solvents in pharmaceuticals are organic volatile chemicals that are used or produced in the manufacture of medicinal substances or excipients, or in the preparation of pharmaceutical products. Residual solvents do not provide therapeutic benefits, therefore should be removed, to the extent possible, to meet ingredients and product specification good manufacturing practice (GMP), or other quality-based requirements. This study utilized headspace gas chromatography mass spectrometry (HS-GC-MS)for the determination of most residual solvents mentioned in United State Pharmacopeia (USP) Class 1 and Class 2 residual solvents. A single rapid method was developed to compare to the USP required 4 individual methods. The system consisted of a VF-624 capillary column and applied selective ion monitoring (SIM). A total of 23 residual solvents can be analyzed in 18 minutes. This study offered a rapid and simple GC-MS method for detecting residual solvents which will be a choice other than the USP Gas chromatography-flame ionization detector (GC-FID) method.