title: Chemical derivatization as a tool for optimizing MS response in sensitive LC-MS/MS bioanalysis and its role in pharmacokinetic studies.
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.
authors.affiliation: Pharmacokinetics Team, Pharmaceutical Research Laboratories, Nippon Kayaku Co. Ltd, 3-31-12, Shimo, Kita-ku, Tokyo, 115-8588, Japan. makoto.niwa@nipponkayaku.co.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Niwa
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D010599:Pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations