THE EFFECT OF THERMAL STERILIZATION AND EXCIPIENTS ON THE STABILITY OF ASCORBIC ACID IN AQUEOUS SOLUTIONS
Objective: To investigate the thermal stability of aqueous solutions of L-ascorbic acid (AA) and its reactions with excipients for the improvement of the injection forms technology.
Methods: The optical rotation – automatic polarimeter Atago POL-1/2. E2lectronic spectra – UV-spectrometer Cary 60 (Agilent). Electrospray tandem mass spectrometry – Sciex X500R QTOF. Unicellular biosensor – Spirotox-test. The statistical methods – packages OriginPro®9.
The results: The polametric and UV-spectral results demonstrate the thermal instability of AA, and the formation of numerous decomposition products that does not obey the laws of stationary kinetics. The optical activity of injection forms of AA differs from not heated model solutions with the same concentration and pH value. Monitoring of model solutions by the LC-ESI-MS/MS method made it possible to characterize the nature of AA thermal decomposition products. Thermodynamic calculations, polarimetric measurements and evaluation of biological activity (Spirotox-test) indicate that AA and sulfite-ion as excipient interact by the redox mechanisms. Specific rotation and Spirostomum ambigua lifetime change as the system becomes more complex after excipients addition and depends on D/H ratio according isotopic kinetic effect.
Conclusion: Heat treatment of L-ascorbic acid solutions in the presence of sulfur (IV) compounds as excipients is accompanied by the formation of products with known or unexplored individual and combined toxicity, as indicates the need to adjust the technology for the ascorbic acid injection forms producing.
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