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), 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.

Direct drug analysis from oral fluid using medical swab touch spray mass spectrometry

“…By contrast, Δ 9 -THC and buprenorphine are detectable at concentrations in the range of hundreds of ng mL −1 and improvement is required to meet official cut-off values, despite the fact that oral fluid concentrations >1 µg mL −1 have been reported for Δ 9 -THC shortly after smoking marijuana [43,44] and for buprenorphine during opiate withdrawal treatment periods. In situations in which the analytical performance for a particular analyte is not satisfactory, a wide portfolio of off-line reactions and on-line derivatization reactions can be used to increase the ionization efficiency and reach lower limits of detection [29,45,46]. …”

Direct drug analysis from oral fluid using medical swab touch spray mass spectrometry

“…By contrast, Δ 9 -THC and buprenorphine are detectable at concentrations in the range of hundreds of ng mL −1 and improvement is required to meet official cut-off values, despite the fact that oral fluid concentrations >1 µg mL −1 have been reported for Δ 9 -THC shortly after smoking marijuana [43,44] and for buprenorphine during opiate withdrawal treatment periods. In situations in which the analytical performance for a particular analyte is not satisfactory, a wide portfolio of off-line reactions and on-line derivatization reactions can be used to increase the ionization efficiency and reach lower limits of detection [29,45,46]. …”

A sensitive, simple and robust LC–MS/MS method for the simultaneous quantification of seven androgen- and estrogen-related steroids in postmenopausal serum

“…Selection of the derivatization reagent is determined by the ionization efficiency of the resulting derivatized steroid [6,7]. Derivatization for GC-MS/MS for the simultaneous assay of many analytes also improves the specificity by changing their chemical and physical properties such as chemical structure, polarity and molecular weight.…”

High-Performance Liquid Chromatographic Determination of Cefalexin Monohydrate and Kanamycin Monosulfate with Precolumn Derivatization

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Direct drug analysis from oral fluid using medical swab touch spray mass spectrometry

“…By contrast, Δ 9 -THC and buprenorphine are detectable at concentrations in the range of hundreds of ng mL −1 and improvement is required to meet official cut-off values, despite the fact that oral fluid concentrations >1 µg mL −1 have been reported for Δ 9 -THC shortly after smoking marijuana [43,44] and for buprenorphine during opiate withdrawal treatment periods. In situations in which the analytical performance for a particular analyte is not satisfactory, a wide portfolio of off-line reactions and on-line derivatization reactions can be used to increase the ionization efficiency and reach lower limits of detection [29,45,46]. …”

A sensitive, simple and robust LC–MS/MS method for the simultaneous quantification of seven androgen- and estrogen-related steroids in postmenopausal serum

“…Selection of the derivatization reagent is determined by the ionization efficiency of the resulting derivatized steroid [6,7]. Derivatization for GC-MS/MS for the simultaneous assay of many analytes also improves the specificity by changing their chemical and physical properties such as chemical structure, polarity and molecular weight.…”

High-Performance Liquid Chromatographic Determination of Cefalexin Monohydrate and Kanamycin Monosulfate with Precolumn Derivatization

“……”

Direct drug analysis from oral fluid using medical swab touch spray mass spectrometry

“…By contrast, Δ 9 -THC and buprenorphine are detectable at concentrations in the range of hundreds of ng mL −1 and improvement is required to meet official cut-off values, despite the fact that oral fluid concentrations >1 µg mL −1 have been reported for Δ 9 -THC shortly after smoking marijuana [43,44] and for buprenorphine during opiate withdrawal treatment periods. In situations in which the analytical performance for a particular analyte is not satisfactory, a wide portfolio of off-line reactions and on-line derivatization reactions can be used to increase the ionization efficiency and reach lower limits of detection [29,45,46]. …”

A sensitive, simple and robust LC–MS/MS method for the simultaneous quantification of seven androgen- and estrogen-related steroids in postmenopausal serum

“…Selection of the derivatization reagent is determined by the ionization efficiency of the resulting derivatized steroid [6,7]. Derivatization for GC-MS/MS for the simultaneous assay of many analytes also improves the specificity by changing their chemical and physical properties such as chemical structure, polarity and molecular weight.…”

High-Performance Liquid Chromatographic Determination of Cefalexin Monohydrate and Kanamycin Monosulfate with Precolumn Derivatization

“……”