ABSTRACT
Investigations by reversed-phase HPLC into the stability of ethacrynic acid in buffered aqueous solutions containing either sodium or ammonium ions showed that the extent of degradation was influenced both by the species and concentration of the cation. A reported incompatibility between ethacrynic acid and the ammonium ion, attributed to the influence of the ammonium ion on an equilibrium existing between ethacrynic acid and one of its known degradation products, was shown to be due to the generation of an additional degradation product in ammonium-containing solutions only. This product was isolated and identified. Different pathways of degradation were shown to be operative in sodium- and ammonium-containing solutions. The addition of formaldehyde or a formaldehyde scavenger (hydroxyammonium chloride) was found to influence the rate of loss of ethacrynic acid, but the decomposition products provided no evidence for the existence of the reported equilibrium.
ABSTRACT
An accurate, reproducible, and specific reversed-phase high-performance liquid chromatographic (HPLC) system was developed for the determination of ethacrynic acid and its degradation products. The method was used in stability studies of the drug in the solid state, in solution, and in dosage forms. Three degradation products were isolated by preparative chromatography and identified by several techniques, principally NMR and MS. TLC Rt and HPLC response factors are quoted. A degradation scheme consistent with the observed stability profiles is proposed.
