化學衍生技術在氣相層析質譜儀法分析濫用藥物上的應用──概念性回顧   全文下載

Chemical Derivatization for the Analysis of Drugs by GC-MS — A Conceptual Review

化學衍生技術應用於氣相層析質譜儀（GC/MS）分析濫用藥物的目的在於：(1) 將待測物之特性官能基衍生轉換成適於層析環境之產物；(2)改善層析分離效果、提高層析效率或創立層析機制；(3) 降低偵測極限或輔助待測物結構之剖析；(4) 結合待測物之特殊結構型態來達成層析的效果。倘若待測物具有酸、鹼或高極性之官能基而不易揮發或易與管柱中之矽醇基（silanol group）或系統中之污染物發生可逆或不可逆反應時，則可經由化學衍生方法予以改善。對掌異構物（enantiomers）於層析分析法中，可使用鏡像試劑（chiral reagent）將鏡像異構物轉變成非鏡像異構物（diastereomers）後，再採用非鏡像分離管柱（achiral columns）分離。適當的化學衍生可將檢體中主要待測物滯留時間（retention time）分佈至可接受之範圍內。經由化學衍生可引進某些特定的元素或官能基以提高偵測訊號或產生特性離子而改進定性與定量的效果。常用的化學衍生劑種類包含：矽烷化反應（silylation）、醯化反應（acylation）及烷化反應（alkylation），文中並包括簡述與實例。

Drugs are often chemically derivatized prior to their GC-MS analysis for the following reasons: (a) to bring the analytes to the chemical forms that are more compatible to the chromatographic environment; (b) to create a separation mechanism or to maximize resolution efficiency; (c) to improve detection or structural elucidation effectiveness; or (d) to make use of the analytes’ specific structural features for analyticl needs. Analytes that are strongly acidic, basic or with functional groups, that may not vaporize or may interact with (irreversibly or reversibly) silanol groups or contaminating compounds present in the chromatographic system, can be more effectively analyzed after chemical derivatization. Enantiomers can be chromatographically resolved by achiral columns after being converted into diastereomers using chiral reagents; derivatization may also bring the retention time of the targeted analytes to a more desirable range. Introduction of certain elements or groups through chemical derivatization may enhance the detector’s response or generate mass spectra helpful to the elucidation of the analytes’ structural features. In conclusion, commonly used derivatization reagents for silylation, acylation, and alkylation are summarized along with comments on some practical considerations.