Prediction of the stability of octreotide in a mixed infusion.

The purpose of this study was to predict the stability of octreotide in a mixed infusion containing sodium bisulfite (SBS). In aqueous solution the hydrolysis of octreotide was found to be accelerated by pH, and by increasing concentrations of SBS. Equations for the degradation rate constants (kobs) of pH and SBS were derived. The fractional rate constants were estimated by the nonlinear least-squares method (quasi-Newton method using the solver in Microsoft Excel) at 25°C. The activation energy (Ea) and frequency factor (A) were calculated using the Arrhenius equation. The pH of the mixed infusion was estimated using the pH characteristic (PHC) curve. From these results, an equation was derived giving the residual ratio (%) of octreotide at any time after mixing an infusion containing SBS at any temperature in the pH range 4.0-7.0. A high correlation was shown to exist between the estimated and determined residual ratios (%).