Methylprednisolone and its related substances in freeze dried powders for injections

Abstract

In this work behavior of active pharmaceutical substances - methylprednisolone (in a form of methylprednisolone sodium succinate) in finished pharmaceutical dosage form - freeze dried powder for injections was examined. The goal was to evaluate the chemical stabilities of methylprednisolone sodium succinate packaged in dual chamber vial, as a specific container closure system. The effect of different parameters: temperature, moisture and light were monitored. USP method for assay was used to determine concentrations of methylprednisolone, as a sum of the concentration of methylprednisolone esters (17-hydrogen succinate and 21-hydrogen succinate) and free methylprednisolone. HPLC method was used for stability evaluation of active substance and related substances determination. Four main degradation products were noted. Temperature has a major impact on degradation process and appearance of 3 degradation products (impurities B, C and D), while the presence of light caused increasing content of impurity A. Identification of impurity B, C and D has been done using mass and NMR spectroscopy as well. All three substances are related substances of methylprednisolone.