Parenteral formulation and thermal degradation pathways of a potent rebeccamycin based indolocarbazole topoisomerase I inhibitor.

The development of a practical and pharmaceutically acceptable parenteral dosage form of 1 is described. A cosolvent formulation strategy was selected to achieve the necessary human dose of 1 for administration via intravenous infusion. The final market formulation of 1 chosen for commercial development and Phase II clinical supplies was the topoisomerase inhibitor dissolved in a 50% aqueous propylene glycol solution vehicle with 50mM citrate buffered to pH 4. The thermal degradation pathways of 1 in this aqueous propylene glycol vehicle in the pH range of 3-5 were determined by relative kinetics and degradation product identification using LC/MS, LC/MS/MS, and NMR analysis. The primary mode of degradation of 1 in this aqueous cosolvent formulation is hydrolysis affording the anhydride 2 (in equilibrium with the dicarboxylic acid 3) and release of the hydrazine diol side chain 11. Subsequent oxidative degradation of 11 occurs in several chemical steps which yield a complicated mixture of secondary reaction products that have been structurally identified.

Direct deposition of gold nanoparticles onto polymer beads and glucose oxidation with H2O2.

Gold nanoparticles (Au NPs) were deposited directly from aqueous solution of diethylenediaminegold(III) complex onto polymer beads commercially available, such as poly(methyl methacrylate) (PMMA), polystyrene (PS), and polyaniline (PANI) without surface modification. The dropwise addition of NaBH4 to reduce Au(III) was found to be very effective to obtain small Au0 NPs with a narrow size distribution except for PANI. The catalytic performance of Au NPs deposited on polymer beads for H2O2 decomposition and glucose oxidation with H2O2 were more significantly affected by the kinds of polymer supports than by the size of Au NPs. The equimolar oxidation of glucose with H2O2 could be operated by controlling the decomposition rate of H2O2 over Au/PMMA.