A fully validated HPLC-UV detection method associated with color variation control for the evaluation of the long term stability of calcium levofolinate solutions in polyolefin infusion bags and in polypropylene syringes in dose banding conditions

PurposeThe aim of this study was to develop and validate a HPLC stability indicating assay for evaluating the calcium levofolinate long-term stability at standardized rounded doses in polyolefin (POF) infusion bags and in polypropylene syringes.MethodsDiluted calcium levofolinate infusion solutions were aseptically prepared by further dilution of calcium levofolinate stock solution with dextrose 5% in POF infusion bags (268 mL) at banded doses of 160 mg, 300 mg, and 400 mg or in polypropylene syringes (10 mL) at 25 mg banded dose. The POF bags and the syringes were stored under refrigeration (5°C ± 3°C) in the dark. Microbiological, physical and chemical stabilities were evaluated.ResultsThe long-term stability of calcium levofolinate at banded doses 160 mg, 300 mg, 400 mg in POF infusion bags was confirmed for respectively 15 weeks, 18 weeks and 19 weeks. For syringes, for a 25 mg banded dose, this long-term stability was confirmed for 20 weeks. Microbiological tests performed were negative.ConclusionsA simple, accurate and stability-indicating HPLC method was developed to determine calcium levofolinate concentrations in dose-banding conditions associated with color variation investigation. This study supports a centralized production of calcium levofolinate in accordance with the studied conditions.