LC with atmospheric pressure ionization MS is essential to a large number of quantitative bioanalyses for a variety of compounds, especially nonvolatile or highly polar compounds. However, in many instances, weak ionization, poor LC retention and instability of certain analytes hinder the development of the LC-MS/MS method. Chemical derivatization has been used for different classes of analytes to improve their ionization efficiency, chromatographic separation and chemical stability. This work presents an overview of chemical derivatization methods that have been applied to the quantitative LC-MS/MS analyses of nine classes of molecules, including aldehydes, amino acids, bisphosphonate drugs, carbohydrates, carboxylic acids, nucleosides and their associated analogs, steroids, thiol-containing compounds and vitamin D metabolites, in biological matrices.
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