Quinapril undergoes a significant degradation in the solid state, especially in the presence of humidity, temperature and pharmaceutical excipients. Since dissolution increases the degradation, hydrolytic reactions are among the most common processes involved in drug degradation. Improving the knowledge regarding drug stability, especially concerning the critical factors that can influence the stability of the active substance in solutions, such as the temperature, the pH and the concentration of catalytic species usually acids or bases is essential for pharmaceutical use; the aim of this study was therefore to develop a new chromatographic method for rapidly and accurately assess the chemical stability of pharmaceutical dosage in acidic, neutral and alkaline media at 80°C according to the ICH guidelines. Ultra High Performance Liquid Chromatography (UPLC) coupled to electrospray ionization tandem mass spectrometry was used for the rapid and simultaneous analysis of quinapril and its by-products. Separation was achieved using a BEH C18 column and a mixture of acetonitrileammonium hydrogencarbonate buffer (pH 8.2; 10 mM) (65:35, v/v) with a flow rate of 0.4 mL/min as a mobile phase. This method allowed the drug by-products profiling, identification, structure elucidation and quantitative determination of by-products under stress conditions. The developed method also provides the determination of the kinetic rate constants for the degradation of quinapril and the formation of its major by-products. Kinetic study and the structure elucidation of by-products allow the development of a complete model including degradation pathway observed under all tested conditions.