Reductive destruction of dacarbazine, procarbazine hydrochloride, isoniazid, and iproniazid

Abstract

Reductive destruction of dacarbazine, procarbazine hydrochloride, isoniazid, and iproniazid using nickel-aluminum alloy in basic solution is described. Solutions of dacarbazine 10 mg/mL were prepared by adding dacarbazine 100 mg, citric acid 100 mg, and mannitol 50 mg to 10 mL of water. Aqueous solutions of procarbazine hydrochloride 10 mg/mL were prepared from commercially available capsules, and aqueous solutions of isoniazid 10 mg/mL and iproniazid 5 mg/mL were prepared from powdered drug. Reductive destruction of drugs was accomplished by mixing each solution with an equal volume of 1 M potassium hydroxide solution and adding 1 g of nickel-aluminum alloy for each 20 mL of basified solution. The resulting mixtures were stirred for 20 hours (96 hours for iproniazid) and analyzed by high-performance liquid chromatography and gas chromatography for the presence of residual drug and degradation products. Dacarbazine solutions were also subjected to destruction by photolysis and by oxidation using potassium permanganate in sulfuric acid, and the results were compared with those obtained by reductive destruction. All reaction mixtures were tested for mutagenicity in Salmonella strains. All drugs subjected to reductive destruction were completely degraded to the limits of detection of the assay and produced only nonmutagenic reaction mixtures. The only acceptable results for dacarbazine were obtained by the reductive destruction method. Reduction of dacarbazine, procarbazine hydrochloride, isoniazid, and iproniazid with nickel-aluminum alloy in dilute base appears to be a good method for the destruction of these toxic compounds.