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The Role of Mass Spectrometry in Biomarker Discovery and Measurement

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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 review, 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.

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

Document Type: Research Article

Affiliations: Greenfield Laboratories, B-220-2, Eli Lilly and Company, 2001 W. Main St., Greenfield, IN 46140,USA.

Publication date: July 1, 2006

More about this publication?
  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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