PHARMACEUTICAL APPLICATION OF LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY .2. ION CHROMATOGRAPHY ION-SPRAY MASS-SPECTROMETRIC CHARACTERIZATION OF ALENDRONATE

The trihydrate of alendronate sodium (MK-0217) is an important bisphosphonate drug for the treatment of a variety of bone diseases. Determination and characterization of this compound in dosage formulations is challenging since it has no chromophore, and as a highly polar and thermally labile compound, it is not amenable to electron impact mass spectrometry. Ion chromatography coupled with an ion spray mass detector (IC-ISP-MS) in the negative ionization mode was developed and applied to the characterization of this compound. Under these conditions alendronate (m/z 248, [M - H](-), M = parent alendronic acid) was readily observed. The anion can form cluster anions with acid molecules including that of the alendronic acid in the gas phase, which is a distinguishing feature of the IC-ISP-MS spectrum. IC-ISP-MS-MS study of the anion shows that cleavage of the C-P bond(s) is the dominant fragmentation pathway(s) of the anion, characteristic of its structure.