Degradation kinetics and mechanism of N6-[(dimethylamino)methylene]mitomycin C in aqueous solutions.

The degradation of N6-[(dimethylamino)methylene]mitomycin C, a semisynthetic analogue of mitomycin C, was studied in aqueous solution. The compound degraded rapidly and followed pseudo-first-order kinetics in both acidic (pH less than 5) and basic pH greater than or equal to 9) media. In the near-neutral pH region, however, biphasic kinetics were observed. At the pH of maximum stability (6.5), 10% activity was lost after approximately 6 h at 22 degrees C. Citrate and phosphate species were catalytic at pH 6.5. Spectrophotometric and HPLC methods were used to elucidate the degradation mechanism at pH 7-9. Under these conditions, equilibrium addition of one water molecule into the amidine side chain occurred, followed by parallel formation of mitomycin C and N6-(formyl)mitomycin C. The latter compound subsequently hydrolyzed to mitomycin C.