A kinetic study of the chemical stability of the antimetastatic ruthenium complex NAMI-A

NAMI-A is a novel ruthenium complex with selective activity against cancer metastases currently in Phase I clinical trials in The Netherlands. The chemical stability of this new agent was investigated utilizing a stability-indicating reversed-phase high performance liquid chromatographic assay with ultraviolet detection and ultraviolet/visible light spectrophotometry. The degradation kinetics of NAMI-A were studied as a function of pH, buffer composition, and temperature. Degradation of NAMI-A follows first-order kinetics at pH<6 and zero-order kinetics at pH ≥6. A pH-rate profile, employing rate constants extrapolated to zero buffer concentration, was constructed, demonstrating that NAMI-A is most stable in pH region 3–4. The degradation rate is not significantly affected by specific buffer components. Storage temperature strongly influences the degradation rate. [Copyright &y& Elsevier]