A high performance liquid chromatography method associated with Arrhenius based kinetics for the evaluation of the long term stability of calcium levofolinate solutions in ready to use polypropylene syringes

Calcium Levofolinate (CaLev) storage stability in a glucose solution was monitored over time to determine the effect of its concentration on reaction kinetics of degradation in polypropylene syringes at standardized dose 4 mg, 12 mg and 25 mg. Syringes were stored at 5, 25, 37, and 45 °C for up to 8 months and degradation was quantified by high-performance liquid chromatography (HPLC) over time. The chemical stability was also evaluated through pH and osmolality monitoring. The value of activation energy Ea of Arrhenius-based kinetic model was the lowest for the 0.4 mg/mL solution (75.00 kJ/mol). CaLev stability was thus dependent on the initial concentration value, with the 0.4 mg/mL CaLev solutions having an increased reaction rate constant (0.00466 day−1) compared to the 1.2 mg/mL (0.00279 day−1) and 2.5 mg/mL (0.00217 day−1) solutions attributed to differences in degradation pathway. The fundamental reaction kinetics of CaLev reported in this study provide a basis for evaluated the long term stability of the 10 mL polypropylene syringes at three standard doses (4 mg, 12 mg, 25 mg) at the two most commonly used storage temperatures in a pharmacy department i.e., 4 °C and 25 °C