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Ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry for robust, high-throughput quantitative analysis of an automated metabolic stability assay, with simultaneous determination of metabolic data

Authors

  • Desmond O'Connor,

    Corresponding author
    1. Merck Sharp & Dohme Research Laboratories, Department of Medicinal Chemistry (Drug Metabolism Section), Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    • Merck Sharp & Dohme Research Laboratories, Department of Medicinal Chemistry (Drug Metabolism Section), Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK.
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  • Russell Mortishire-Smith,

    1. Merck Sharp & Dohme Research Laboratories, Department of Medicinal Chemistry (Drug Metabolism Section), Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
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  • Denise Morrison,

    1. Merck Sharp & Dohme Research Laboratories, Department of Medicinal Chemistry (Drug Metabolism Section), Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
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  • Amy Davies,

    1. Merck Sharp & Dohme Research Laboratories, Department of Medicinal Chemistry (Drug Metabolism Section), Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
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  • Maria Dominguez

    1. Merck Sharp & Dohme Research Laboratories, Department of Medicinal Chemistry (Drug Metabolism Section), Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
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Abstract

The application of ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC/TOFMS) for high-throughput analysis of a 96-well plate based metabolic stability assay has been investigated. Full-scan data were acquired, with run times of 2.5–3.5 min, from which narrow window extracted ion chromatograms were generated, producing quantitative data for the test compound equivalent to that obtained by high-performance liquid chromatography with tandem mass spectrometric detection on a triple quadrupole instrument (HPLC/MS/MS). Sensitivity and mass accuracy were maintained over the analysis of >300 samples. Additionally, the UPLC/TOFMS datasets obtained gave access to metabolic route information, at no cost in terms of sensitivity for the test compound. Copyright © 2006 John Wiley & Sons, Ltd.

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