The Role of Mass Spectrometry in Biomarker Discovery and Measurement

Bradley      L. Ackermann; John      E. Hale; Kevin      L. Duffin

doi:10.2174/138920006777697918

Abstract

Recent advances in the biological and analytical sciences have led to unprecedented interest in the discoveryand quantitation of endogenous molecules that serve as indicators of drug safety, mechanism of action, efficacy, and dis-ease state progression. By allowing for improved decision-making, these indicators, referred to as biomarkers, can dra-matically improve the efficiency of drug discovery and development. Mass spectrometry has been a key part of biomarkerdiscovery and evaluation owing to several important attributes, which include sensitive and selective detection, multi-analyte analysis, and the ability to provide structural information. Because of these capabilities, mass spectrometry hasbeen widely deployed in search for new markers both through the analysis of large molecules (proteomics) and smallmolecules (metabonomics). In addition, mass spectrometry is increasingly being used to support quantitative measurementto assist in the evaluation and validation of biomarker leads. In this revi ew, the dual role of mass spectrometry for bio-marker discovery and measurement is explored for both large and small molecules by examining the key technologies andmethods used along the continuum from drug discovery through clinical development.

Keywords: Biomarker discovery, biomarker quantitation, proteomics, metabonomics, liquid chromatography massspectrometry (LC/MS), gas chromatography mass spectrometry (GC/MS), stable isotope internal standard, matrix assisted laserdesorption ionization, electrospray ionization