Rationality Evaluation of Packaging Materials and Study on Impurity Profiling of Cilnidipine Preparations by HPLC-Q-TOF/MS

Abstract

Background: The rationality of cilnidipine tablets and capsules with four different pharmaceutical packaging materials was evaluated, and the structure of photodegradation impurities was analyzed by LC-Q-TOF. Materials and Methods: The impurity profiling of commercial cilnidipine tablets and capsules was analyzed by LC-Q-TOF for the further improvement of official monograph in pharmacopoeias and the source of the impurities was investigated. The contents of photodegradation impurities were analyzed by HPLC, and remarkable difference in the formation of the photodegradation impurities in cilnidipine tablets and capsules with four different pharmaceutical packaging materials was observed. The shading effect of the four packaging materials was investigated by UV-Vis spectrophotometer and a remarkable difference was detected, which might be responsible for the difference in the formation of photodegradation products. The structures of photodegradation products were further characterized by LC-Q-TOF MS/MS. Five impurities in commercial cilnidipine tablets and capsules were separated and identified based on the high resolution MS/MS data. Results: The obtained results revealed that the impurity III was derived from the ethanol solution of cilnidipine when it was exposed to light, and the impurity II was produced when the cilnidipine powder was exposed to light directly. The concentrations for 50% reduction of impurity II and impurity III on the Chinese hamster lung cells (CHL) with CellTiter-Glo method were studied and the results indicated that the cytotoxicity of impurity II and impurity III on CHL cells was larger than cytotoxicity of cilnidipine. Conclusion: On the basis of our study, we suggested that the pharmaceutical packaging materials of cilnidipine tablets should be modified.