Reaction monitoring of platinum(II) complex-5 '-guanosine monophosphate adduct formation by ion exchange liquid chromatography/electrospray ionization mass spectrometry

Cisplatin and four structurally related platinum(II) complexes were incubat ed with guanosine 5 ' -monophosphate (5 ' -GMP) in water at 37 degreesC. Th e adduct formation reactions were monitored with cation-and anion-exchange liquid chromatography/electrospray ionization mass spectrometry. In additio n to mono- and bis-adducts of guariosine 5 ' -monophosphate with the platin um(II) complexes, other molecular species, presumably with a binuclear stru cture (two platinum(II) centres), were detected in the reaction mixtures, w hich have not been reported previously, indicating an unexpected complexity of adduct formation. Anion-exchange chromatography revealed the presence o f isomers of two complexes which presumably result from the restricted rota tion at the platinum-N-7 (5 ' -GMP) bonds. All reaction products were chara cterized in both the positive and negative ion modes. Furthermore, prelimin ary kinetics and half-times of complex formation were investigated for cisp latin and two other platinum(fl) complexes, monitoring the relative concent rations of free 5 ' -GMP and of mono- and bis-GMP adducts as a function of time (250 h) using an internal standard protocol with thymidine 5 ' -monoph osphate. Copyright (C) 2001 John Wiley & Sons, Ltd.