A new strategy for ionization enhancement by derivatization for mass spectrometry

Liquid chromatography–mass spectrometry (LC–MS) using atmospheric pressure ionization is drastically different from hitherto available analytical methods used to detect polar analytes. The electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources of MS have contributed to the advancement of LC–MS and LC–MS/MS techniques for the analysis of biological samples. However, one major obstacle is the weak ionization of some analytes in the ESI and APCI techniques. In this review, we introduce high-sensitivity methods using several derivatization reagents for ionization enhancement. We also present an overview of chemical derivatization methods that have been applied to small molecules, such as amino acids and steroids, in biological samples.