本试验建立了气相色谱串联质谱法测定苯甲酸阿格列汀中基因毒性杂质苯甲醛、苯甲醇、2- 氰基溴苄和三正丁胺的分析方法。采用6％氰丙基苯-94％二甲基硅氧烷为固定相(DB-624，0.32 mm×30 m，1.8 μm)，用多反应监测模式检测。结果显示4 种待测物均具有较好的线性关系，相关系数r ≥ 0.999 2，检测限均为2 ng/ml，平均回收率在90％～ 100％，且供试品溶液、杂质对照品溶液和系统适用性溶液在室温(25 ℃ ) 放置12 h 内稳定。3 批生产规模样品中均未检出2- 氰基溴苄、苯甲醛、苯甲醇和三正丁胺。说明本试验建立的分析方法灵敏度高、分离度好、结果准确，可有效分离并测定苯甲酸阿格列汀中的4 种潜在毒性杂质，为其质量控制提供保障。
Abstract
In this study, a GC-MS/MS method was established for the simultaneous determination of benzaldehyde, benzyl alcohol, 2-cyanobenzyl bromide and tri-n-butylamine in alogliptin benzoate. The method was performed on a DB-624 capillary column(6％ cyanide propylbenzene-94％ dimethylsiloxane copolymer, 0.32 mm×30 m, 1.8 μm) and the analytes were detected with MS/MS in multiple reaction monitoring mode. The results showed that there was a good linearity(r≥0.999 2). The limits of detection all were 2 ng/ml and their average recoveries were 90％ - 100％. The test solution, reference solution and system suitability solution were stable for at least 12 h at 25 ℃. 2-Cyanobenzyl bromobenzyl, benzaldehyde, benzyl alcohol and tri-n-butylamine were not detected in three batches of alogliptin benzoate. With high sensitivity, good resolution and accuracy, the method could be reliably and effectively used in the determination of the above four kinds of trace impurities in alogliptin benzoate as well as provided a guarantee for the quality control of alogliptin benzoate.
关键词
苯甲酸阿格列汀 /
气相色谱串联质谱 /
基因毒性杂质 /
含量测定
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Key words
alogliptin benzoate /
GC-MS/MS /
genotoxic impurities /
determination
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参考文献
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脚注
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基金
江苏省博士后科研资助计划项目(2018K265C)
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