Compatibility and stability of ademetionine 1,4-butanedisulfonate injection mixed with fructose and glucose diluents and pilot study of long-term storage impurities by LC-MS/MS

Abstract

Abstract Fructose injection is occasionally used to dilute ademetionine 1,4-butanedisulfonate injection for patients who cannot receive glucose or sodium chloride injections in clinical settings. Since our PIVAS staff reported that discoloration occurred after ademetionine 1,4-butanedisulfonate dissolved with fructose injection, this study aims to investigate the stability of ademetionine 1,4-butanedisulfonate in fructose and glucose solutions. Ademetionine 1,4-butanedisulfonate was purchased and diluted with fructose or glucose injection for compatibility testing. The solutions were maintained under various conditions for different periods of time, after which the concentration of ademetionine 1,4-butanedisulfonate and other impurities was analyzed. The chemical structures of unknown impurities were further investigated by liquid chromatography-tandem mass spectrometry. The analytical method was validated and was deemed to be suitable for the analyses in this study. Compatibility tests indicated that ademetionine 1,4-butanedisulfonate is sensitive to temperature, illumination, and pH. When diluted with fructose or glucose, the concentration of ademetionine 1,4-butanedisulfonate decreased over time. The contents of impurities increased accordingly. Additionally, an unknown impurity was identified, speculated to be a hydroxyl oxidation product of ademetionine based on the LC-MS/MS results. Both fructose and glucose injections can be used as diluents for ademetionine 1,4-butanedisulfonate, and the resulting mixture remains stable for up to 8 h after preparation.

Keywords

• Ademetionine
• Fructose
• Compatible stability
• High-performance liquid chromatography
• Liquid chromatography-tandem mass spectrometry