Many cyclic peptides are formed using a disulfide bond to increase their conformational rigidity; this provides receptor selectivity and increased potency. However, degradation of the disulfide bond in formulation can lead to a loss of structural stability and biological activity of the peptide. Therefore, the objective of this study was to study the stability of peptide 1 (cyclo(1,4)-Cys-Gly-Phe-Cys-Gly-OH). This cyclic peptide was synthesized using Boc strategy via solution-phase peptide synthesis and purified using semi-preparative HPLC. The accelerated stability studies of the cyclic peptide were conducted in buffer solutions at pH 1.0-11.0 with controlled ionic strengths at 70 degrees C. The pH-rate profile shows that the peptide has an optimal stability around pH 3.0 with a V-shape between pH 1.0 and 5.0. Two small plateaus are observed at pH 5.0-7.0 and pH 8.0-10.0, indicating hydrolysis on different ionized forms of the cyclic peptide. One product was observed at acidic pH due to peptide bond hydrolysis at Gly2-Phe3. The number of degradation products increases as the pH increases from neutral to basic, and most of the degradation products at neutral and basic pH are derived from the degradation at the disulfide bond. (c) 2006 Wiley-Liss, Inc.