Determination of Impurities in Perampanel Bulk Drugs by High- Performance Liquid Chromatography and Gas Chromatography
Background: High-Performance Liquid Chromatography (HPLC) method has been used to detect related impurities of perampanel. However, the detection of impurities is incomplete, and the limits of quantification and detection are high. A sensitive, reliable method is badly needed to be developed and applied for impurity detection of perampanel bulk drug. Objective: Methodologies utilising HPLC and Gas Chromatography (GC) were established and validated for quantitative determination of perampanel and its related impurities (a total of 10 impurities including 2 genotoxic impurities). Methods: The separation was achieved on a Dikma Diamonsil C18 column (250 mm 4.6 mm, 5 μm) with the mobile phase of 0.01 mol/L potassium dihydrogen phosphate solution (A) and acetonitrile (B) in gradient elution mode. The compound 2-bromopropane was determined on an Agilent DB-624 column (0.32 mm 30 m, 1.8 μm) by electron capture detector (μ-ECD) with split injection ratio of 1:5 and proper gradient temperature program. Results: Both HPLC and GC methods were established and validated to be sensitive, accurate and robust according to the International Council for Harmonization (ICH) guidelines. The methods developed were linear in the selected concentration range (R2≥0.9944). The average recovery of all impurities was between 92.6% and 103.3%. The possible production mechanism of impurities during the synthesis and degradation processes of perampanel bulk drug was also discussed. Five impurities were analyzed by liquid chromatography–mass spectrometry (LC-MS). Moreover, two of them were simultaneously characterized by LC-MS, IR and NMR. Conclusion: The HPLC and GC methods were developed and optimized, which could be applied for quantitative detection of the impurities, and further stability study of perampanel.
危险品化学品经营许可证（带存储）