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Updated: May 25, 2026

Untargeted Metabolomics from Biological Sources Using Ultraperformance Liquid Chromatography-High Resolution Mass Spectrometry (UPLC-HRMS)
Published on: May 20, 2013
Chemical derivatization as a tool for optimizing MS response in sensitive LC-MS/MS bioanalysis and its role in
1Pharmacokinetics Team, Pharmaceutical Research Laboratories, Nippon Kayaku Co. Ltd, 3-31-12, Shimo, Kita-ku, Tokyo, 115-8588, Japan. makoto.niwa@nipponkayaku.co.jp
Abstract:
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.
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