Effect of sodium bisulphate on the stability of octreotide acetate: compatibility study with dexamethasone injection

Abstract

Background: Although several dexamethasone phosphate preparations are commercially available and frequently administered with octreotide acetate, their compatibility remains unknown. Aim: We investigated the effect of pH and sodium bisulphate on the stability of octreotide acetate. Measurement design: Octreotide acetate percentage was measured 3 and 10 days after it was mixed with 2 dexamethasone phosphate preparations containing different concentrations of sodium bisulphate as an additive, and in one that did not contain sodium bisulphate. Solutions were also analysed after they were prepared using phosphate buffer to achieve pH values of 4.0, 7.0, and 9.0. The initial octreotide acetate concentration was 41.7 g/mL. High−performance liquid chromatography was used for measurement. Results: The octreotide acetate percentage in the mixture with dexamethasone phosphate without sodium bisulphate was maintained at 95% for up to 10 days. However, mixing octreotide acetate with the other 2 agents resulted in a significant decrease to 85%. The octreotide acetate percentage was ＜90% after sodium bisulphate−containing solution was stored at room temperature under light−protected conditions for 3 days. The percentage of octreotide acetate in the pH 7.0 solution was ＜90% three days after preparation; however, in the pH 4.0 solution, it was maintained at 95% for up to 10 days. Conclusions: Our results suggest that octreotide acetate is hydrolysed in the presence of sodium bisulphate, leading to a decrease in the percentage of octreotide acetate in the solution, which can be avoided using sodium bisulphate−free dexamethasone phosphate preparations. Palliat Care Res 2013; 8(2): 177−83

Stability of octreotide acetate decreases in a sodium bisulfate concentration-dependent manner: compatibility study with morphine and metoclopramide injections

“…A significant decrease was observed in the concentration of OCT on day 0, and this has been attributed to the progression of hydrolysis at the time of the measurement due to sample preparation time. Further decreases may occur in OCT concentration depending on other factors, such as the pH, temperature and exposure to light; 9 19 therefore, mixing should be avoided under these conditions. Judgements regarding expiry dates (from immediately after preparation to the completion of its use) are varied when the final SBS concentration is 0.1 mg/mL.…”

“…6–8 We previously investigated incompatibilities with dexamethasone (DEX) injections, which are sold as an ethical drug, and demonstrated that OCT concentrations were maintained for 10 days in a mixture with a DEX injection that did not contain SBS but were significantly decreased in a mixture with a SBS-containing DEX injection. 9 However, the concentrations of SBS that have a clinical influence have not yet been determined, and the stability of these drugs, other than DEX, remains unclear.…”

Effect of pH and Additives on the Compatibility between Vancomycin and Furosemide Injections

“…However, diŠerent additives have been reported to aŠect the stability of injections between original injections and generic injections. 5,6) In addition, far less information is provided for generic injections than for original injections. In hospitals, therefore, clinical pharmacists often use the data from the original injections when using generic injections.…”

Prediction of the Stability of Octreotide in a Mixed Infusion

“…Asahara et al 20) reported that insulin was easily degraded by disulphide bond cleavage in the presence of SBS. Although octreotide also contains a disulfide bond, Tanabe et al 21) reported that degradation of octreotide was mainly due to hydrolysis not to cleavage of the disulphide bond in the molecule. Our results confirm this conclusion and show that octreotide seems to be easily hydrolysed.…”