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

Abstract

Cisplatin and four structurally related platinum(II) complexes were incubated with guanosine 5'-monophosphate (5'-GMP) in water at 37 degrees C. The adduct formation reactions were monitored with cation- and anion-exchange liquid chromatography/electrospray ionization mass spectrometry. In addition to mono- and bis-adducts of guanosine 5'-monophosphate with the platinum(II) complexes, other molecular species, presumably with a binuclear structure (two platinum(II) centres), were detected in the reaction mixtures, which have not been reported previously, indicating an unexpected complexity of adduct formation. Anion-exchange chromatography revealed the presence of isomers of two complexes which presumably result from the restricted rotation at the platinum-- N-7 (5'-GMP) bonds. All reaction products were characterized in both the positive and negative ion modes. Furthermore, preliminary kinetics and half-times of complex formation were investigated for cisplatin and two other platinum(II) complexes, monitoring the relative concentrations 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'-monophosphate.