Isotope dilution mass spectrometry for absolute quantification in proteomics: concepts and strategies

Isotope dilution mass spectrometry is a reference technique for quantitative analysis, given that it combines the sensitivity and selectivity of MS instruments with the precision and accuracy associated with the use of internal standards. Isotope-labeled proteins are the optimal internal standards for quantitative proteomics as they closely mimic the behavior of their natural counterparts during the analytical process. A major complication of isotope dilution mass spectrometry proteomics is the technical difficulty of obtaining these internal standards, especially in studies where a high number of proteins have to be quantified simultaneously. In this paper, we review some of the characteristics of the isotope dilution mass spectrometry approach, its benefits in terms of reliability and quality control in targeted proteomic analysis and the different strategies developed for its application in proteomics.