Abstract
Protein kinases inhibitors or, more generally, signal transduction inhibitors (STIs) can be used to treat diseases in which deregulation of the protein kinase activity plays a role, such as in cancer. A wide variety of drugs has been developed and/or is under investigation to act as protein kinase inhibitors, especially in tyrosine kinase inhibition. The bioanalysis of STIs has received considerable attention in the past 20 years. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) in selected-reaction monitoring (SRM) mode is the method-of-choice in such studies. In several of these studies from us and others, structures are proposed for the product ions applied in SRM. A critical review of these proposed structures is presented using accurate-m/z data, which we have now generated with a linear-ion-trap-Orbitrap hybrid mass spectrometer. This led to adaptation and new structural proposals of 18 product ions for 13 STIs. Our investigation endorses the power of accurate-m/z analysis in structure elucidation of product ions in bioanalytical LC-MS-MS studies and for which the SRM mode in tandem-quadrupole instruments is apparently less suitable.