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.
Lin, D.-L.; Wang, S.-M.; Wu, C.-H.; Chen, B.-G.; and Liu, R.H.
"Chemical derivatization for the analysis of drugs by GC-MS - A conceptual review,"
Journal of Food and Drug Analysis: Vol. 16
, Article 1.
Available at: https://doi.org/10.38212/2224-6614.2373