Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is currently the most powerful system in biomedical analysis. At the same time, chemical derivatization is a useful technique to enhance the detection sensitivity of non- or poorly ionizable molecules in LC-MS/MS. Derivatization improves the ionization efficiency, the chromatographic separation and/or the chemical stability. This review presents an overview of the recent development of chemical derivatization reagents and reactions for the quantitative analysis of xenobiotic and endogenous molecules such as pharmaceuticals, amino acids, peptides, proteins, steroids, biomarkers and industrial products by LC-MS.
