酒石酸唑吡坦片中杂质的色谱-质谱结构鉴定

发布时间：2018-03-03 19:00

  本文选题：安眠药　切入点：失眠症　出处：《药物分析杂志》2017年06期 　论文类型：期刊论文

【摘要】：目的:采用LC-MS对酒石酸唑吡坦片中的杂质进行结构鉴定。方法:通过酸、碱、高温、氧化和光照对酒石酸唑吡坦片中的杂质进行富集,采用液相色谱-超高分辨飞行时间质谱对未知杂质进行鉴定,色谱柱为C_(18)(2.1 mm×100 mm,1.9μm),流动相为10 mmol·L~(-1)乙酸铵溶液-甲醇-乙腈(53∶23∶18),采用ESI正离子模式进行质谱扫描。结果:结合酒石酸唑吡坦的处方工艺初步推测了6个杂质的化学结构。杂质1:4-(二甲胺基)-3-(6-甲基-2-对甲苯基咪唑并[1,2-a]吡啶-3-基)-4-氧代丁酸;杂质4:N-甲基-2-(6-甲基-2-对甲苯基咪唑并[1,2-a]吡啶-3-基)乙酰胺;杂质5:2-羟基-N,N-二甲基-2-(6-甲基-2-对甲苯基咪唑并[1,2-a]吡啶-3-基)乙酰胺;杂质6:N,N-二甲基-2-(6-甲基-2-对甲苯基咪唑并[1,2-a]吡啶-3-基)-2-氧代乙酰胺;杂质7:N,N-二甲基-2-(6-甲基-2-对甲苯基-2,3-二氢咪唑并[1,2-a]吡啶-3-基)乙酰胺;杂质8:6-甲基-2-对甲苯基咪唑并[1,2-a]吡啶-3-甲醛。它们都具有6-甲基-2-苯基咪唑并[1,2-a]吡啶的母核。结论:超高分辨飞行时间质谱技术能够有效地用于药物中杂质的鉴定,酒石酸唑吡坦杂质研究可为其质量控制和工艺优化提供参考依据。
[Abstract]:Objective: to identify the impurities in zolpidem tartrate tablets by LC-MS. Methods: the impurities in zolpidem tartrate tablets were enriched by acid, alkali, high temperature, oxidation and illumination. Unknown impurities were identified by liquid chromatography-ultrahigh resolution time-of-flight mass spectrometry. The chromatographic column was Che _ (18) ~ (18) mm 脳 10 ~ (10) mmol 路L ~ (-1) mmol 路L ~ (-1) 路L ~ (-1) acetonitrile-methanol-acetonitrile 53: 23: 18. The mass spectrometry was performed by ESI positive ion mode. Results: the chemical structures of the six impurity were preliminarily inferred by combining the prescription of zolpidem tartrate with 10 mmol 路L ~ (-1) acetonitrile solution. The impurity is 1: 4-dimethylamino-6-methyl-2-methyl-2-methyl-imidazolido [1za2-a] pyridine -3-methyl-4-oxobutyric acid; Impurity 4: N- methyl-2-methyl-2-methyl-2-methyl-2-methyl-4-methyl-imidazolidazolido [1 (2-a) pyridine-3-yl) acetamide; impurity 5: 2-hydroxy-N-dimethyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-4-methyl-imidazolyl [1 (2-a] pyridyl-3-yl) acetamide; Impurity 6: N- N- dimethyl-2-oxoacetamide; impurity 7: N- N- dimethyl-2-oxoacetamide; impurity 7: N-, N-dimethyl-2-oxoacetamide; impurity 7: N-, N-dimethyl-2-oxoacetamide; impurity 7: N-, N-dimethyl-2-oxoacetamide; impurity 7: N-, N-dimethyl-2-oxo-6-methyl-2-dihydroimidazolium and [12-a] pyridine-3-yl) acetamide; Impurity 8: 6- methyl-2- p-methylimidazo [1h2a] pyridine-3-formaldehyde. They all have the parent nucleus of 6-methyl-2-phenyimidazo [1h2a] pyridine. Conclusion: ultrahigh resolution time-of-flight mass spectrometry can be used to identify impurities in drugs. The study on the impurity of zolpidem tartrate can provide reference for its quality control and process optimization.
【作者单位】： 湖南省食品药品检验研究院;
【基金】：2015年湖南省食品药品监督管理局食品药品安全科技项目,编号湘食药科G201507
【分类号】：O657.63;R927.1
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本文编号：1562281