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

Int J Pharm. 2002 Nov 6;248(1-2):239-46. doi: 10.1016/s0378-5173(02)00460-x.

Abstract

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.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics*
  • Dimethyl Sulfoxide / analogs & derivatives*
  • Dimethyl Sulfoxide / chemistry*
  • Dimethyl Sulfoxide / pharmacokinetics*
  • Drug Stability
  • Neoplasm Metastasis / prevention & control*
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacokinetics*
  • Pharmacokinetics
  • Ruthenium / chemistry
  • Ruthenium / pharmacokinetics
  • Ruthenium Compounds

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Ruthenium Compounds
  • imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III)
  • Ruthenium
  • Dimethyl Sulfoxide