| 杜益,张营,汪玉馨,孟长虹,潭力,张玫,陆益红.右兰索拉唑N-氧化物杂质测定及毒性分析[J].中国药品标准,2018,19(1):32-37 |
| 右兰索拉唑N-氧化物杂质测定及毒性分析 |
| Determination of Nitrogen Oxides in Dexlansoprazole and Their Toxicity Prediction |
| 投稿时间：2017-10-09 修订日期：2018-02-08 |
| DOI： |
| 中文关键词: 右兰索拉唑 杂质 液质联用 毒性预测 |
| 英文关键词: Dexlansoprazole impurities LC-MS Toxicity prediction |
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| 摘要点击次数: 575 |
| 全文下载次数: 14 |
| 中文摘要: |
| 摘要 目的：建立液相-质谱联用法（Liquid chromatography mass spectrometry，LC-MS）测定右兰索拉唑中N-氧化物的方法并对N-氧化物的毒性进行预测。方法：使用X-Bridge C18（250×4.6mm，5μm）柱，流动相A为0.02M醋酸铵溶液，流动相B为乙腈，梯度洗脱，采用电喷雾离子源，选择性正离子检测模式。利用ADMET Predictor软件对N-氧化物的毒性进行预测。结果：右兰索拉唑N-OX亚砜、N-OX砜、N-OX硫化物各杂质之间的分离度符合要求。线性浓度范围分别为12.92～206.68 ng·mL-1、12.31～196.92 ng·mL-1和13.15～210.40ng·mL-1，检测限分别为0.23 ng·mL-1、0.14 ng·mL-1和0.14 ng·mL-1，定量限分别为2.57 ng·mL-1、1.73 ng·mL-1和1.25 ng·mL-1。各杂质回收率，精密度以及24 h内稳定性均符合要求，可以用于上述杂质的测定。软件预测表明：各N-氧化物均有不同程度的肝毒性和致癌性，N-OX硫化物毒性最高。检测结果显示：三批供试品均检出N-OX亚砜，检出量分别为12.75 ng·mg-1、8.28 ng·mg-1和9.13 ng·mg-1，均未检出N-OX砜和N-OX硫代物。结论：本文所建立的LC-MS方法方便、快捷、灵敏度高，可用于右兰索拉唑N-氧化物检查。N-氧化物作为潜在毒性杂质在生产过程及质量控制中需要加以关注。 |
| 英文摘要: |
| AbstractObjective：To establish a liquid chromatography mass spectrometry method for the determination of nitrogen oxides in Dexlansoprazole and predict their toxicity. Methods：Chromatography was performed on a X-Bridge C18(250 mm×4.6 mm，5 μm), the mobile phase composition (A) was 0.02 M ammonium acetate aqueous and (B) was acetonitrile, gradient elution was employed. Single ion monitoring (SIM) with positive electrospray ionization in MS was used for quantification.The ADMET Predictor was used to predict the toxicity of nitrogen oxides. Results：The method shows good resolution of nitrogen oxides of Dexlansoprazole. The liner range of each impurities were from12.92to 206.68 ng·mL-1, from 12.31to 196.92 ng·mL-1and from 13.15to 210.40 ng·mL-1,with detection limit of 0.23 ng·mL-1, 0.14 ng·mL-1,and 0.14 ng·mL-1，with quantitation limit of 2.57 ng·mL-1, 1.73 ng·mL-1and 1.25 ng·mL-1respectively. The method has high recovery, good precision and accuracy, and excellent stability in 24h.All nitrogen oxides may have hepatotoxicity and carcinogenicity, and the toxicity of N-OX sulfides is the highest one. The results showed that N-OX sulphoxide in three batches were 12.75 ng·mg-1, 8.28 ng·mg-1 and 9.13 ng·mg-1, respectively，while N-OX sulphone and N-OX sulphide were not detected. Conclusions： The method is simple, accurate and specific, it is suitable for the detection on nitrogen oxides of Dexlansoprazole. As a potential toxic substances,?Nitrogen oxides need to be concerned in the production process and quality control. |
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