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Electrospray tandem mass spectrometry of alendronate analogues: fingerprints for characterization of new potential prodrugs
Author(s) -
Hardouin Julie,
Guénin Erwann,
Malosse Christian,
Caron Michel,
Lecouvey Marc
Publication year - 2008
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.3610
Subject(s) - chemistry , tandem mass spectrometry , electrospray ionization , electrospray , mass spectrometry , prodrug , molecule , dissociation (chemistry) , amine gas treating , protein mass spectrometry , chromatography , combinatorial chemistry , tandem , organic chemistry , biochemistry , materials science , composite material
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‐MS n ) 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 (HPO 2 , ROP(OH) 2 and ROPO(OH) 2 ), where R = H, C 6 H 5 , or CH 3 OC 6 H 5 . These fingerprints will be of great value for differentiating alendronate from its potential prodrugs in complex biological mixtures. Copyright © 2008 John Wiley & Sons, Ltd.