Abstract
The invention of new ionization techniques namely electrospray ionization and matrix‐assisted laser desorption/ionization combined with the development of novel mass spectrometer analyzers and evolving isotope‐ratio mass spectrometry have fueled the presence and use of modern mass spectrometric methodologies in many bioanalytical laboratories. Consequently, over the past two decades, a steadily increasing number of quantitative methods employing stable isotope labeling techniques have been reported, including prominent examples of methods to determine differential expression of proteins in disease studies, new‐born screening for metabolic disorders, and tracing drugs or dietary compounds and their respective metabolites. Labeling biomolecules for quantitative studies using mass spectrometry has several challenges, including potentially insufficient labeling efficiency, ionization suppression, chromatographic separation of labeled and non‐labeled compounds, and isotope exchange with the environment. It is not surprising that method development to minimize or eliminate existing limitations represents a very active and dynamic research area. Copyright © 2007 John Wiley & Sons, Ltd.