Chemical derivatization as a tool for optimizing MS response in sensitive LC–MS/MS bioanalysis and its role in pharmacokinetic studies

Chemical derivatization is the only technique that directly affects the physicochemical property of an analyte in an LC–MS/MS assay platform. On the other side, current MS instruments are extremely sensitive, but still their absolute sensitivity is analyte-dependent. In this review, first, difficulty in analyzing neutral compounds and introducing acidity/basicity and/or proton affinity will be described. Second, the sweet spot of the conventional MS ion source across clogP values is presented. Third, optimization of hydrophilicity/hydrophobicity by derivatization is described. Lastly, development of a new derivatizing reagent specifically designed for LC–MS/MS is described and its significance in pharmacokinetic analysis is discussed. LC–MS/MS...

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