The role of mass spectrometry in biomarker discovery and measurement.
Recent advances in the biological and analytical sciences have led to unprecedented interest in the discovery and quantitation of endogenous molecules that serve as indicators of drug safety, mechanism of action, efficacy, and disease state progression. By allowing for improved decision-making, these indicators, referred to as biomarkers, can dramatically improve the efficiency of drug discovery and development. Mass spectrometry has been a key part of biomarker discovery 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 has been widely deployed in search for new markers both through the analysis of large molecules (proteomics) and small molecules (metabonomics). In addition, mass spectrometry is increasingly being used to support quantitative measurement to assist in the evaluation and validation of biomarker leads. In this review, the dual role of mass spectrometry for biomarker discovery and measurement is explored for both large and small molecules by examining the key technologies and methods used along the continuum from drug discovery through clinical development.
Ackermann
Bradley L
BL
Drug Disposition, Greenfield Laboratories, Eli Lilly and Company, Greenfield, IN 46140, USA. brad.ackermann@lilly.com
Hale
John E
JE
Duffin
Kevin L
KL
D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D040901:Proteomics / Q000639:trends; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D049490:Systems Biology / Q000639:trends; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends
D015415:Biomarkers; D004364:Pharmaceutical Preparations