Photostability profiles of the experimental antimetastatic ruthenium complex NAMI-A.
NAMI-A is a novel ruthenium complex with selective activity against metastases currently in Phase I clinical trials in The Netherlands. The photostability of this new agent in solid state and in solution has been investigated utilizing a stability-indicating reversed-phase high performance liquid chromatographic (HPLC) assay and ultraviolet/visible (UV/VIS) light spectrophotometry. In solid state, NAMI-A proved to be photostable. In solution, however, the compound degraded rapidly, in a pH-independent manner in the pH range of 2-5. At alkaline pH, the degradation rate was higher than at acidic pH. The type of buffer species had little influence. NAMI-A concentration was inversely related to the photostability. Addition of photostabilizers (5% DMSO, 2% benzyl alcohol, 0.001% curcumin) marginally increased the half-life. NAMI-A's photostability in solution was influenced to the greatest extent by addition of an alcohol, with the least polar solvent system (50% propylene glycol) providing the most stable medium. Based on the presented results, it is recommended to store NAMI-A solutions in the dark.
Bouma
Marjan
M
Slotervaart Hospital/The Netherlands Cancer Institute, Department of Pharmacy and Pharmacology, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands.
Nuijen
Bastiaan
B
Jansen
Martine T
MT
Sava
Gianni
G
Bult
Auke
A
Beijnen
Jos H
JH
D000970:Antineoplastic Agents / Q000032:analysis / Q000737:chemistry*; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry*; D004355:Drug Stability; D008029:Lighting / Q000009:adverse effects*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009942:Organometallic Compounds / Q000032:analysis / Q000737:chemistry*; D012428:Ruthenium / Q000032:analysis / Q000737:chemistry*; D017975:Ruthenium Compounds
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D012428:Ruthenium; D004121:Dimethyl Sulfoxide