The integration of liquid chromatography-mass spectrometry (LC-MS) with derivatization is a relatively new and unique strategy that could add value and could enhance the capabilities of LC-MS-based technologies. The derivatization process could be carried out in various analytical steps, for example, sampling, storage, sample preparation, HPLC separation, and MS detection. This review presents an overview of derivatization-based LC-MS strategy over the past 10 years and covers both the general principles and applications in the fields of pharmaceutical and biomedical analysis, biomarker and metabolomic research, environmental analysis, and food-safety evaluation. The underlying mechanisms and theories for derivative reagent selection are summarized and highlighted to guide future studies.
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