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Advances in mass spectrometry applied to pharmaceutical metabolomics

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Abstract

Metabolomics, also referred to in the literature as metabonomics, is a relatively new systems biology tool for drug discovery and development and is increasingly being used to obtain a detailed picture of a drug’s effect on the body. Metabolomics is the qualitative assessment and relative or absolute quantitative measurement of the endogenous metabolome, defined as the complement of all native small molecules (metabolites less than 1,500 Da). A metabolomics study frequently involves the comparative analysis of sample sets from a normal state and a perturbed state, where the perturbation can be of any nature, such as genetic knockout, administration of a drug, or change in diet or lifestyle. Advances in mass spectrometry (MS) technologies including direct introduction or in-line chromatographic separation modes, ionization techniques, mass analyzers, and detection methods have provided powerful tools to assess the molecular changes in the metabolome. This review focuses on advances in MS pertaining to the analytical data generation for the main metabolomics methods, namely, fingerprinting, nontargeted, and targeted approaches, as they are applied to pharmaceutical drug discovery and development.

Three-dimensional image of a liquid chromatography-mass spectrometry (LC-MS) profile.

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Acknowledgement

The authors would like to thank Serhiy Hnatyshyn for helpful discussions around data analysis and for providing one of the illustrations.

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Authors and Affiliations

  1. Research and Development - Discovery Analytical Sciences, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT, 06492, USA

    Dieter M. Drexler

  2. Research and Development - Discovery Analytical Sciences, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ, 08543, USA

    Michael D. Reily

  3. Research and Development - Discovery Analytical Sciences, Bristol-Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ, 08534, USA

    Petia A. Shipkova

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  1. Dieter M. Drexler
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  2. Michael D. Reily
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  3. Petia A. Shipkova
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Correspondence to Dieter M. Drexler.

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Published in the special issue Advances in Analytical Mass Spectrometry with guest editor Maria Careri.

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Drexler, D.M., Reily, M.D. & Shipkova, P.A. Advances in mass spectrometry applied to pharmaceutical metabolomics. Anal Bioanal Chem 399, 2645–2653 (2011). https://doi.org/10.1007/s00216-010-4370-8

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