Stability of carboplatin and oxaliplatin in their infusion solutions is due to self-association

Anthony J. Di Pasqua, Deborah J. Kerwood, Yi Shi, Jerry Goodisman, James C. Dabrowiak

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Carboplatin and oxaliplatin are commonly used platinum anticancer agents that are sold as ready-to-use aqueous infusion solutions with shelf lives of 2 and 3 years, respectively. The observed rate constants for the hydrolysis of these drugs, however, are too large to account for their long shelf lives. We here use electrospray-trap mass spectrometry to show that carboplatin and oxaliplatin are self-associated at concentrations in their ready-to-use infusion solutions (∼27 mM and 13 mM, respectively) and, as expected, when the drug concentration is reduced to more physiologically relevant concentrations (100 μM and 5 μM, respectively) the association equilibrium is shifted in favor of the monomeric forms of these drugs. Using 1H NMR we measure the intensity of the NH resonance of the two symmetry-equivalent NH3 molecules of carboplatin, relative to the intensity of the γ-methylene CH resonance, as a function of total drug concentration. Then, by fitting the data to models of different molecularity, we show that the association complex is a dimer with a monomer-dimer association constant of K (M-1) = 391 ± 127. The work presented here shows that carboplatin and oxaliplatin mainly exist as association complexes in concentrated aqueous solution, a property that accounts for the long term stability of their ready-to-use infusion solutions, and that these association complexes may exist, to some extent, in the blood after injection.

Original languageEnglish (US)
Pages (from-to)4821-4825
Number of pages5
JournalDalton Transactions
Issue number18
StatePublished - May 14 2011

ASJC Scopus subject areas

  • Inorganic Chemistry


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