Electrospray tandem mass spectrometry of alendronate analogues: fingerprints for characterization of new potential prodrugs.
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.
Hardouin
Julie
J
Laboratoire de Biochimie des Protéines et Protéomique, Université Paris XIII, UMR CNRS 7033, 74 rue Marcel Cachin, 93017 Bobigny cedex, France. hardouin@smbh.univ-paris13.fr
Guénin
Erwann
E
Malosse
Christian
C
Caron
Michel
M
Lecouvey
Marc
M
D019386:Alendronate / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D050071:Bone Density Conservation Agents / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D011355:Prodrugs; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D050071:Bone Density Conservation Agents; D011355:Prodrugs; D012997:Solvents; D009584:Nitrogen; D019386:Alendronate