Stability and compatibility of the investigational antimetastatic ruthenium complex NAMI-A in infusion systems and its hemolytic potential

NAMI-A (imidazolium trans-imidazole dimethylsulfoxide tetrachlororuthenate (III)) is a novel antimetastatic ruthenium complex currently undergoing Phase I clinical trials. It is pharmaceutically formulated as a lyophilized product to be reconstituted and diluted before infusion. The aim of this study was to determine the reconstitution and dilution fluid of choice, and to investigate the stability and compatibility of NAMI-A in solution under different storage conditions and with several container materials. Furthermore, the hemolytic potential and buffer capacity of NAMI-A infusion solution were investigated in vitro. Normal saline or Water for Injections (WfI) can be used for reconstitution of NAMI-A, and the reconstituted solution should be diluted with normal saline to infusion concentration immediately after dissolution if stored at room temperature (1 20 - 258C), but can be stored for up to 48 hours at refrigerated conditions (1 2 - 88C). Infusion solutions can be stored for a maximum of four hours at room temperature or 24 hours at refrigerated conditions before administration to the patient. The infusion solutions can be prepared in either glass or PVC containers, although for practical reasons PVC containers are recommended. The infusion solutions are compatible with a PVC infusion system consisting of a PVC container, PVC infusion line, and needle. Furthermore, NAMI-A infusion solutions have a low buffer capacity and do not cause hemolysis in vitro. Therefore, no pain or hemolysis upon infusion of NAMI-A in the clinical setting is expected.