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Chemical Reagents and Derivatization Procedures in Drug Analysis

Pharmaceuticals and Drugs

  1. Neil D. Danielson1,
  2. Patricia A. Gallagher2,
  3. James J. Bao3

Published Online: 29 SEP 2008

DOI: 10.1002/9780470027318.a1905.pub2

Encyclopedia of Analytical Chemistry

Encyclopedia of Analytical Chemistry

How to Cite

Danielson, N. D., Gallagher, P. A. and Bao, J. J. 2008. Chemical Reagents and Derivatization Procedures in Drug Analysis. Encyclopedia of Analytical Chemistry. .

Author Information

  1. 1

    Miami University, Oxford, OH, USA

  2. 2

    Environmental Protection Agency, Cincinnati, OH, USA

  3. 3

    Tianjin University, Tianjin, China

Publication History

  1. Published Online: 29 SEP 2008


This article describes both pre- and postcolumn derivatization chemistry used in conjunction with either chromatography or capillary electrophoresis (CE) to facilitate the determination of drugs. Generally, only prederivatization is used in gas chromatography (GC), principally to enhance the volatility, temperature stability, and/or detectability. The GC section considers derivatization of drugs by reagent class: alkylation, acylation, and silylation. The GC sample-handling section describes an approach that combines the extraction and derivatization steps together. Both pre- and postcolumn derivatization are common approaches for high-performance liquid chromatography (HPLC) and many of these methods have been adapted for CE. Derivatization for HPLC is often directed toward aliphatic amines, carboxylic acids, or alcohols that are difficult to detect at low levels by absorbance, luminescence, or electrochemical means. In addition, small hydrophilic molecules upon prederivatization are often converted into larger more hydrophobic compounds, making reversed-phase HPLC easier or even feasible. The HPLC section considers derivatization of drugs based on the following types: alkaloids, amines, antibiotics, barbiturates, carbonyl compounds and carboxylic acids, catecholamines, hydroxy compounds, steroids, and sulfur compounds. For the GC and HPLC sections, tables are included, giving the structures of the more important derivatizing agents, the analytes, and the corresponding reaction products. A brief rationale for derivatization chemistry with CE concludes this article. For CE, derivatization is often done to improve detectability as the path length for absorbance detection is very short and fluorescence can be effective using laser-based systems.