Chemical Reagents and Derivatization Procedures in Drug Analysis

Abstract

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), principallyto 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 which 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 type: 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 since the path length for absorbance detection is very short and fluorescence can be effective using laser‐based systems.

Derivatization Reactions and Reagents for Gas Chromatography Analysis

“…Alkylation reactions can also be used to prepare ethers, thioethers and thioesters, Nalkylamines, amides and sulphonamides (Danielson, 2000). In general, the products of alkylation are less polar than the starting materials because active hydrogen has been replaced by an alkyl group.…”

Bioanalytical methods for the determination of synthetic cannabinoids and metabolites in biological specimens

“…In SCs analysis, it seems essential to include a derivatisation step prior to GC analysis to increase detectability and stability of compounds and help to improve analytical efficiency [105]. SCs are organic compounds containing active and polar functional groups, and are allowed to react with different types of derivatisation reagents.…”

Spectrophotometric determination of ranitidine hydrochloride (RNH) in pharmaceutical formulation using 9-fluorenylmethyl chloroformate (FMOC-Cl)

“…Both primary and secondary amines were derivatized with FMOC-Cl before separation by reversed-phase HPLC with UV detection at 254 nm. Several pharmaceutical compounds have been determined through this approach 23 .…”