An isocratic stability-indicating HPLC assay method was developed to quantitate ethacrynic acid in solution formulations. Utilizing the method, the main thermal, hydrolytic, and one of the oxidative degradation products could be separated. The structure of the separated degradation products was confirmed by negative ion-mode HPLC-MS. The hydrolytic results confirmed the previously reported sequence of the formation of the dimeric Michael adduct. At the lower temperature, hydrogen peroxide can react with ethacrynic acid to form the epoxide derivative (7). At the higher temperature, several other oxidation products were also formed. The validated analytical method can be used to quantitate ethacrynic acid in a solution formulation in the 0.5-500 µg/mL concentration range.