气相色谱法测定非布司他原料药中的基因毒性杂质盐酸羟胺
Determination of the genotoxic impurity hydroxylamine hydrochloride in Febuxostat raw materials by gas chromatography
李彬 1李丽婉2
作者信息
- 1. 开封市中医院,河南 475000
- 2. 上海药明康德新药开发有限公司,上海 200131
- 折叠
摘要
目的:建立了气相色谱衍生化法测定非布司他中潜在基因毒性杂质盐酸羟胺的含量.方法:用环己酮将盐酸羟胺衍生为环己酮肟,通过气相色谱进行测定.色谱柱为安捷伦DB-624 色谱柱(30 m×0.53 mm,3 μm);检测器为氢火焰离子化检测器(FID),检测器的温度260℃;进样口温度为230℃;高纯氮气为载气,恒流模式,流速为 1.5 ml/min;色谱柱的升温程序为:起始温度 55℃,维持 2 min,以 20℃/min的升温速率升温至 95℃,维持 2 min,再以 40℃/min的升温速率升温至250℃,维持20 min.进样量为 1 μl;分流比为 5:1.结果:盐酸羟胺在 0.2247～2.696 μg/ml范围内,浓度与峰面积线性关系良好(r=0.9997);平均回收率为99.24％～106.59％之间,RSD为 2.29％.结论:本方法简单,准确度高,重现性好,可用于非布司他原料药中盐酸羟胺的质量控制.
Abstract
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.
关键词
盐酸羟胺/非布司他/潜在基因毒性杂质/气相色谱/衍生化法Key words
hydroxylamine hydrochloride/febuxostat/protentional genotoxic impurity/gas chromatography/derivati-zation method引用本文复制引用
出版年
2024
NETL
NSTL
万方数据