Methylprednisolone and its related substances in freeze dried powders for injections

In this work, the behavior of the active pharmaceutical substances methylprednisolone (in a form of methylprednisolone sodium succinate) in fi- nished pharmaceutical dosage form, i.e., freeze-dried powder for injections, was examined. The goal was to evaluate the chemical stabilities of methylpre- dnisolone sodium succinate packaged in a dual chamber vial, as a specific con- tainer closure system. The effect of different parameters: temperature, moisture and light were monitored. The method proposed by United States Pharma- copeia was used to determine concentrations of methylprednisolone, as the sum of the concentration of methylprednisolone esters (17-hydrogen succinate and 21-hydrogen succinate) and free methylprednisolone. The HPLC method was used for stability evaluation of the active substance and determination of re- lated substances. Four main degradation products were registered. Temperature has a major impact on the degradation process with the appearance of 3 degra- dation products (impurities B, C and D), while the presence of light caused an increasing content of impurity A. Identification of impurity B, C and D has been realized using mass and NMR spectroscopy. All three substances are substances related to methylprednisolone.