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Novel MS solutions inspired by MIST

    ,
    Jonathan L Josephs

    Department of Biotransformation, Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, NJ, 08540, USA

    ,
    Mohammed Jemal

    Bioanalytical and Discovery Analytical Sciences, Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, NJ 08540, USA

    ,
    Mark Arnold

    Bioanalytical and Discovery Analytical Sciences, Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, NJ 08540, USA

    &
    W Griffith Humphreys

    Department of Biotransformation, Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, NJ, 08540, USA

    Published Online:https://doi.org/10.4155/bio.10.83

    To improve patient safety and to help avoid costly late-stage failures, the pharmaceutical industry, along with the US FDA and International Committee on Harmonization (ICH), recommends the identification of differences in drug metabolism between animals used in nonclinical safety assessments and humans as early as possible during the drug-development process. LC–MS is the technique of choice for detection and characterization of metabolites, however, the widely different LC–MS response observed for a new chemical entity (NCE) and its structurally related metabolites limits the direct use of LC–MS responses for quantitative determination of NCEs and metabolites. While no method provides completely accurate universal response, UV, corona charged aerosol detection (CAD), radioactivity, NMR and low-flow (<20 µl/min) nanospray approaches provide opportunities to quantify metabolites in the absence of reference standards or radiolabeled material with enough precision to meet the needs of early clinical development.

    Papers of special note have been highlighted as: ▪ of interest

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