Probing the stability of serum protein-ruthenium(III) drug adducts in the presence of extracellular reductants using CE.

A CE kinetic assay was developed to study the stability of the adducts of a novel ruthenium(III)-based anticancer agent with serum proteins under simulated reductive physiological conditions. Formation of the reactive Ru(II) species and their release from the serum proteins are thought to play an important role in the mode-of-action of indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) which has successfully finished a clinical phase I study. The CE method was adapted, in zone electrophoresis and affinity CE modes, to make obvious that such transformation would take place in the hypoxic tumor tissue rather than in the bloodstream.