A highly sensitive LC-MS/MS method for the trace level determination of genotoxic impurities, Cinnamyl chloride and Benzhydryl Chloride, in Cinnarizine drug substance is developed and validated.
A simple SIM mode of operation is employed for Mass Spectrometric detection.
Trace level LOD and LOQ values are: 0.49 and 1.47 ppm for Cinnamyl Chloride and 0.55 and 1.67 ppm for Benzhydryl chloride respectively.
Developed method is successfully applied to drug products.
A highly sensitive LC-MS/MS method for the trace level determination of genotoxic impurities, Cinnamyl chloride and Benzhydryl chloride, in Cinnarizine drug substance was developed and validated. Chromatographic separation was successfully achieved on Atlantis d C18 column with dimensions 150× 4.6 mm and particle size: 5 μm. 0.1% Trifluoroacetic acid in water and 100 % acetonitrile was used as mobile phases with gradient mode of elution at 1.0 mL/min flow rate. Mass spectroscopic detection was carried out with selective ion monitoring (SIM) technique in positive mode at m/z 117 and 167 for Cinnamyl chloride and Benzhydryl chloride respectively. Developed method was proven to be selective, sensitive, and precise for the quantification of potential genotoxic impurities in Cinnarizine by validating as per the regulatory guidelines. The LOD and LOQ values observed for Cinnamyl chloride were 0.49 and 1.47 ppm and for Benzhydryl chloride 0.55 and 1.67 ppm respectively. Precision of the method at LOQ level was shown with good % RSD of 4.21. Method was proven linear from LOQ to 150% level with a correlation of 0.996 and accurate with a range of recovery from 86.4 to 100.8%. This highly sensitive method can be used to control both the genotoxic impurities in Cinnarizine drug substance by LC-MS/MS.Le texte complet de cet article est disponible en PDF.
Keywords : Cinnarizine, Genotoxic impurities, LC-MS/MS, Cinnamyl chloride, Benzhydryl chloride