摘要
本研究通过破坏试验,追踪吉非替尼的降解产物,并对氧化杂质进行合成和定性定量分析。其结构经 ~1 H NMR、^(13)C NMR和MS确证为4-[(3-氯-4-氟)苯胺基]-6-[3-(吗啉-4-基)丙氧基]-7-甲氧基-1-氧代喹唑啉(氧化杂质A)。通过调节流动相配比和pH值,建立了特异性检测吉非替尼片中氧化杂质的HPLC条件。使用C_(18)色谱柱,以乙腈∶1%乙酸铵溶液(用冰乙酸调至p H 6.0)(38∶62)为流动相,检测波长253 nm。氧化杂质A在0.5~2.0μg/ml范围内线性关系良好,定量限为0.15μg/ml。本法能高效准确地测定吉非替尼片中的氧化杂质含量,可为其质量标准的建立提供参考。
The degradation products of gefitinib through stressing test were traced. Among them, the oxidative impurity （named as oxidative impurity A） was synthesized, and then qualitatively and quantitatively determined. Its structure was elucidated by ^1H NMR, ^13C NMR and MS as 4-[（3-chloro-4-fluoro）phenylamino]-7-methoxy-6-[3-（morpholin-4-yl）propoxy] quinazolin-1-oxide. The HPLC method was optimized by changing the mobile phase ratio and pH value of aqueous phase. A Hypersil C18 column was used, with the mobile phase of acetonitrile∶1%ammonium acetate buffer （adjusted to pH 6.0 by acetate acid）（38∶62）, at the detection wavelength of 253 nm. It was linear for oxidative impurity A in the range of 0.5—2.0 μg/ml, with LOQ of 0.15 μg/ml. It indicated that the oxidative impurity in gefitinib tablets could be effectively and accurately determined by the established HPLC method, which provided a reference for the establishment of the quality standard for gefitinib tablets.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2018年第2期224-229,共6页
Chinese Journal of Pharmaceuticals
基金
广东省战略性新兴产业核心技术攻关计划项目(2012A080800012)
