HPIC-UV-ICP-SFMS study of the interaction of cisplatin with guanosine monophosphate.
Interaction of cis-[Pt(NH3)2Cl2] (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 31P and 195Pt. To separate significant interferences from 15N16O+, 14N16O1H+, 12C18O1H+, and 13C17O1H+ on 31P, high-mass resolution (m/deltam = 4,500) 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-.
Hann
S
S
Institute of Chemistry, University of Agricultural Sciences, Vienna, Austria. shann@edv2.boku.ac.at
Zenker
A
A
Galanski
M S
MS
Bereuter
T L
TL
Stingeder
G
G
Keppler
B K
BK
D000970:Antineoplastic Agents / Q000737:chemistry; D002852:Chromatography, Ion Exchange; D002945:Cisplatin / Q000032:analysis* / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry; D004347:Drug Interactions; D006157:Guanosine Monophosphate / Q000032:analysis* / Q000737:chemistry*; D013058:Mass Spectrometry; D010984:Platinum / Q000032:analysis* / Q000737:chemistry
D000970:Antineoplastic Agents; D018736:DNA Adducts; D010984:Platinum; D006157:Guanosine Monophosphate; D002945:Cisplatin