Stability of Octastatin, a Somatostatin Analog Cyclic Octapeptide, in Aqueous Solution

Abstract

ABSTRACTIn this study, the degradation of Octastatin, a cyclic octapeptide analog of somatostatin, was examined as a function of pH, temperature, buffer, and ionic strength by reversed-phase gradient high-performance liquid chromatography. Degradation of Octastatin followed a first-order kinetics. Various buffer species such as acetate, ammonium acetate, citrate, glutamate, phosphate, and borate showed differing effects on the degradation of the octapeptide. Good stability was found in glutamate and acetate buffer of pH 4.0. Degradation of Octastatin was greater in citrate- or phosphate-containing buffers than in glutamate or acetate buffers. With phosphate buffer, higher buffer concentration caused greater degradation, while in acetate buffer, the effect of buffer concentration and ionic strength was negligible. In addition, the degradation of Octastatin was markedly inhibited by increasing the concentration of glutamate buffer. This study allows the prediction of good stability in acetate buffer (0.01 M, pH 4.0) with a t90% of 84.1 days at 20°C.