Determination of Genotoxic Impurities in Perampanel by LC-MS/MS
Objective:To establish a high-performance liquid chromatography-mass spectrometry(LC-MS/MS)method for the determination of the genotoxic impurity 2-(2-oxo-1-phenyl-5-(N-pyridine oxide)-2-yl-1,2-dihydropyridine-3-yl)benzonitrile in perampanel.Methods:The chromatographic conditions were as follows:a C18 column(YMC-Triart C18,2.1 mmx 100 mm,1.9 pm)using 0.05％formic acid aqueous solution(mobile phase A)and acetonitrile(mobile phase B)in gradient elution(0～1 min,10％B;8～10 min,90％B;10.1～12 min,10％B).The flow rate was 0.3 mL/min,injection volume was 5 pL.The mass spectrometry conditions were as follows:electro spray ionization source(ESI+),multistage reaction monitoring(MRM)mode,ion spray voltage of 5 500 V,ion source gas pressure of 344.74 kPa(50 psi),curtain gas pressure of 50 344.74 kPa(50 psi),auxiliary heating gas pressure of 50 344.74 kPa(50 psi),drying gas temperature is 500 ℃,carrier gas flow of 500 L/h,declustering potential of 150 V,collision energy of 27 V,monitoring ion pair of 366.0→273.0 and scanning time of 100 ms.The 0～6.8 min HPLC eluent was entered into the mass spectrometry for detection,and the 6.8～12 min HPLC eluent was cut into the waste.Results:2-(2-oxo-1-phenyl-5-(N-oxidepyridine)-2-yl-1,2-dihydropyridine-3-yl)benzonitrile had good linearity in the range of 3.76～18.80 ng/mL(r=0.998 9),the limits of detection and quantification were 1.13 and 3.38 ng/mL,respectively,and the recovery rate was 85.9％～94.2％,with good stability.It has strong specificity and is suitable for the determination of 2-(2-oxo-1-phenyl-5-(N-oxopyridine)-2-yl-1,2-dihydropyridine-3-yl)benzonitrile content in perampanel.
万方数据
维普
