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

Abstract

PurposeSodium bisulfate is known to affect the stability of octreotide. However, the critical concentration of sodium bisulfate is not known. Therefore, we assessed the critical concentration of sodium bisulfate needed to preserve the stability of octreotide using actual drugs containing sodium bisulfate.MethodsAlthough morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography.ResultsOctreotide concentrations decreased significantly at a sodium bisulfate concentration of 0.1 mg/mL or higher after 10 days when octreotide was mixed with sodium bisulfate solutions at various concentrations. A significant decrease in octreotide concentrations also occurred when it was mixed with morphine and metoclopramide preparations containing sodium bisulfate and stored for 10 days; however, slight decreases were observed in the mixture with both preparations and were within the clinically acceptable range for morphine preparations.ConclusionsThese results indicate that the residual rate of octreotide decreases with time in a sodium bisulfate concentration-dependent manner when octreotide was mixed with morphine or metoclopramide. However, this incompatibility may be clinically acceptable when the final sodium bisulfate concentration is lower than 0.1 mg/mL and the mixed solution is used within 7 days.

Hydrophilic Interaction Liquid Chromatography Coupled with Fluorescence Detection (HILIC-FL) for the Quantitation of Octreotide in Injection Forms

“…In this work, a hydrophilic interaction liquid chromatographic method with fluorescence (HILIC-FL) detection was developed and validated for the quantification of A literature survey revealed various analytical methods for the detection of octreotide. These methods include the determination of octreotide levels in human plasma using ultrahigh-performance liquid chromatography with tandem mass spectrometric detection (UHPLC-MS/MS) [25], the quantification of octreotide acetate in formulation and stability studies in sodium bisulfate using reversed phase liquid chromatography with ultraviolet (UV) detection at 210 nm [26,27], the assessment of octreotide stability under stress conditions via a capillary electrophoresis-mass spectrometric method (CE-MS) [28] and the determination of long-acting release octreotide in human plasma by means of liquid chromatography coupled to tandem mass spectrometry [29]. Reversed-phase highperformance liquid chromatography (RP-HPLC) with UV detection was used to separate poly(ethylene glycol)octreotide derivatives with various molecular weights [30] and also to find optimal conditions to produce mono-poly(ethylene glycol) octreotide [31].…”