Determination of the genotoxic impurity hydroxylamine hydrochloride in Febuxostat raw materials by gas chromatography
Objective:To establish a gas chromatography derivatization method for the determination of hydroxy-lamine hydrochloride,a potentially genotoxic impurity,in febuxostat.Methods:Hydroxylamine hydrochloride was converted into cyclohexanone oxime using cyclohexanone and determined by gas chromatography.The chromatography column was an Agilent DB-624 chromatography column(30 m×0.53 mm×3 μm).The detector was a hydrogen flame ionization detector(FID),with a temperature of 260℃.The inlet temperature was maintained at 230℃.High-purity nitrogen was used as the carrier gas in the constant flow mode with a flow rate of 1.5 ml/min.The heating program of the chromatographic column was as follows:starting at 55℃,maintaining it for 2 min,increasing the temperature at a rate of 20℃/min to 95℃,maintaining it for 2 min,and then increasing the temperature at a rate of 40℃/min to 250℃,and maintaining it for 20 min.The injection volume was 1 μl.The shunt ratio was 5∶1.Results:Hydroxylamine hydrochloride had a good linear relationship with peak areas in the range of 0.2247～2.696 μg/ml(r=0.9997).The average recoveries ranged from 99.24%to 106.59%and the RSD was 2.29%.Conclusion:The method is simple,accurate,and reproducible and can be used for the quality control of hydroxylamine hy-drochloride in febuxostat raw materials.
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