Abstract
Quinapril undergoes a significant degradation in the solid state, specially 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, particularly 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 are essential for pharmaceutical use. The aim of this study was therefore to develop a new chromatographic method for rapidly and accurately assessing the chemical stability of quinapril and to study the mechanism of quinapril degradation in acidic, neutral and alkaline media at 80°C according to the ICH guidelines. Ultra High Performance Liquid Chromatography (UPLC) coupled with electrospray ionization tandem mass spectrometry and/or diode array detector 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 acetonitrile-ammonium hydrogencarbonate buffer (pH 8.2; 10 mM) (65:35, v/v) at a flow rate of 0.4 mL/min as a mobile phase. This method allowed drug byproducts profiling, identification, structure elucidation and quantitative determination 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. A complete model including degradation pathway observed under all tested conditions was proposed according to the kinetic study and the structure elucidation of by-products.
Keywords: Quinapril, stress testing, ICH guideline (Q1A R2), UPLC-MS/MS, degradation products, degradation pathway.
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