HPIC-UV-ICP-SFMS study of the interaction of cisplatin with guanosine monophosphate

Interaction of cis-[Pt(NH3)(2)Cl-2] (cisplatin) with 5'-guanosine monophosphate (5'-GMP) has been investigated for the first time by on-line coupling of high performance ion chromatography (HPIC) to inductively coupled plasma sector field mass spectrometry (ICP-SFMS). The time-dependent reaction course of the cisplatin-5'-GMP system was followed after incubation under simulated physiological conditions by monitoring the decrease in the concentration of 5'-GMP and the increase in the concentration of formed adducts, on the basis of speciation analysis. Because of the two-step mechanism an intermediate mono adduct was observed together with the major product, the bis adduct cis-[Pt(NH3)(2)(GMP)(2)](2-). The data obtained correlated well with those from earlier studies employing orthogonal techniques such as capillary electrophoresis (CE). Furthermore, HPIC-ICP-SFMS provided unambiguous stoichiometric information about the major GMP-adduct. For this purpose the platinum-to-phosphorus ratio was determined by simultaneously measuring P-31 and Pt-195. To separate significant interferences from N-15 O-16(+) (NOH+)-N-14-O-16-H-1, (COH+)-C-12-O-18-H-1, and (COH+)-C-13-O-17-H-1 on P-31, high-mass resolution (m/Deltam = 4500) proved to be mandatory. The P/Pt signal ratio of 2/1 obtained corresponds to the molar ratio in the bis adduct cis-[Pt(NH3)(2)(GMP)(2)](2-).