Degradation of tauromustine (TCNU) in aqueous solutions.

The stability of tauromustine in buffered aqueous solutions was investigated over the pH range 0.9-7.5. The pH rate profile at zero buffer concentration has a specific acid catalytic region at pH below 2, a plateau of pH-independent degradation between pH 2 and 4, and shows a sharp increase in the degradation rate at pH above 4. The activation parameters, the solvent isotope effect and the effect of the dielectric constant on the degradation rate were determined, and possible degradation mechanisms were discussed. The effects of six cyclodextrin (CD) derivatives on the stability of tauromustine in aqueous buffer solutions were investigated. All the CDs tested had some stabilizing effect on the drug at pH 1.98 and 4.06 but they had little or no effect at pH 6.38. Hydroxypropyl-alpha-cyclodextrin (HP alpha CD) had the largest stabilizing effect. Tauromustine degraded about 25 to 50% slower in aqueous buffer solutions containing 2% HP alpha CD compared to buffer solutions containing no CD.