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Electrospray tandem mass spectrometry of alendronate analogues: fingerprints for characterization of new potential prodrugs

Authors

  • Julie Hardouin,

    Corresponding author
    1. Laboratoire de Biochimie des Protéines et Protéomique, Université Paris XIII, UMR CNRS 7033, 74 rue Marcel Cachin, 93017 Bobigny cedex, France
    2. Laboratoire de Chimie Structurale Biomoléculaire - BioMoCeTi, Université Paris XIII, UMR CNRS 7033, 74 rue Marcel Cachin, 93017 Bobigny cedex, France
    • Laboratoire de Biochimie des Protéines et Protéomique, UMR CNRS 7033 (BioMoCeTi), Université Paris 13, 74 rue Marcel Cachin, 93017 Bobigny cedex, France.
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    • These authors contributed equally to this work.

  • Erwann Guénin,

    1. Laboratoire de Chimie Structurale Biomoléculaire - BioMoCeTi, Université Paris XIII, UMR CNRS 7033, 74 rue Marcel Cachin, 93017 Bobigny cedex, France
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    • These authors contributed equally to this work.

  • Christian Malosse,

    1. Laboratoire des Mécanismes Réactionnels, Ecole Polytechnique, CNRS, 91128 Palaiseau, France
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  • Michel Caron,

    1. Laboratoire de Biochimie des Protéines et Protéomique, Université Paris XIII, UMR CNRS 7033, 74 rue Marcel Cachin, 93017 Bobigny cedex, France
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  • Marc Lecouvey

    1. Laboratoire de Chimie Structurale Biomoléculaire - BioMoCeTi, Université Paris XIII, UMR CNRS 7033, 74 rue Marcel Cachin, 93017 Bobigny cedex, France
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Abstract

1-Hydroxymethylene-1,1-bisphosphonic acids (HMBPs) are important drugs for the treatment of a variety of bone diseases. Since these compounds have no chromophore, their detection is challenging and mass spectrometry (MS) appears to be an appropriate sensitive tool. Our work deals with the analysis by electrospray ionization tandem mass spectrometry (ESI-MSn) of the well-known nitrogen-containing HMBP alendronate and of three analogues, considered as potential prodrugs. These four molecules share a common structure with different protecting groups on the phosphonic acid and on the amine functions. We describe the dissociation mechanisms of nitrogen-containing HMBPs in positive ion mode and we compare, in negative ion mode, our results with literature data. In both modes, the dissociations are essentially losses of ROH, and of phosphorus-containing species (HPO2, ROP(OH)2 and ROPO(OH)2), where R = H, C6H5, or CH3OC6H5. These fingerprints will be of great value for differentiating alendronate from its potential prodrugs in complex biological mixtures. Copyright © 2008 John Wiley & Sons, Ltd.

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