High pressure liquid chromatographic investigation of the pH and temperature effect on the solution stability of lisinopril

Abstract

Lisinopril, a new drug substance, is an angiotensin-converting enzyme (ACE) inhibitor. In this study, we investigate the high pressure liquid chromatographic pH effect on the solution stability of lisinopril. Lisinopril solutions of 75 mu g/ml were prepared in various buffer solutions in the range of pH = 2-8. These solutions were heated in an oven at 80 degrees C for various hours. After these periods the solutions were removed and cooled immediately. Then, 10 mu l of the solution was injected into a high pressure liquid chromatographic system containing a Bondapak C18 reversed phase column and a variable wavelength UV - visible absorbance detector. The separation was performed with pH = 5 phosphate buffer - acetonitril - triethylamine (90 : 10 : 0.1) mixture as isocratic mobile phase. The detector was operated at 209 nm. The investigation of the chromatograms; and lisinopril peak areas indicated that pH has a significant effect on the stability of lisinopril in aqueous solution and decomposition rate of lisinopril is increased by the decreasing pH. Pseudo first order rate constants were calculated using the time - log (peak area) plots.