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 > or =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.
Bouma
Marjan
M
Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands. apmbo@slz.nl
Nuijen
Bastiaan
B
Jansen
Martine T
MT
Sava
Gianni
G
Flaibani
Antonella
A
Bult
Auke
A
Beijnen
Jos H
JH
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000493:pharmacokinetics*; D004355:Drug Stability; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D010599:Pharmacokinetics; D012428:Ruthenium / Q000737:chemistry / Q000493:pharmacokinetics; D017975:Ruthenium Compounds
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D012428:Ruthenium; D004121:Dimethyl Sulfoxide