Solution chemistry and analytical characterization of ormaplatin

Ormaplatin is a racemic, platinum(IV), anti-cancer drug which is currently involved in phase 1 clinical trials. Characterizing the purity of ormaplatin represents an analytical challenge for several reasons. These include the lack of solution stability of ormaplatin, its process impurities and solution decomposition products, the strong concentration and pH dependence of various decomposition pathways and solution equilibria and the absence of chromatographic reproducibility. Two independent types of aqueous decomposition pathways have been observed. The first pathway involves the generation of soluble PtIV containing species which remain in equilibrium with the parent material in solution. The second pathway involves the generation of PtII containing materials which tend to be less soluble. The most interesting material in this latter class is probably the chloride bridged mixed valence material which has been characterized structurally by X-ray diffraction. Liquid chromatography and sample handling procedures have been developed which allow for the accurate determination of bulk drug purity, as well as, an understanding of numerous reversible equilibria.