LC-MS-MS测定吡仑帕奈中的遗传毒性杂质

　　

[摘要]目的 建立高效液相色谱-质谱/质谱联用（LC-MS/MS）方法测定吡仑帕奈中的遗传毒性杂质2-(2-氧代-1-苯基-5-(N-氧化吡啶)-2-基-1,2-二氢吡啶-3-基)苯腈。方法 液相色谱条件：选用C₁₈色谱柱（YMC-Triart C₁₈, 2.1*100 mm, 1.9 μm），以0.05%甲酸水溶液为流动相A，乙腈为流动相B，梯度洗脱（0~1 min，10%B；8~10 min，90%B；10.1~12 min，10%B），流速为0.3 ml/min，进样量为5 μl；质谱条件：采用电喷雾离子源（ESI⁺），进行多级反应监测（MRM），离子化电压为5500 V，喷雾气压力为50 psi，气帘气压力为50 psi，辅助加热气压力为50 psi，干燥气温度为500 ℃,载气流速为500 L/h，去簇电压为150 V，碰撞电压为27 V，监测离子对为366.0→273.0，扫描时间为100 ms；质谱程序分2个阶段，即0~6.8 min液相色谱洗脱液进入质谱检测，6.8~12 min液相色谱洗脱液切入废液。结果 2-(2-氧代-1-苯基-5-(N-氧化吡啶)-2-基-1,2-二氢吡啶-3-基)苯腈在3.76~18.80 ng/ml的范围内线性良好（r=0.9989），检测限和定量限分别为1.13 ng/ml和3.38 ng/ml，回收率在85.9%~94.2%，稳定性良好，本研究所建立的方法快速、灵敏、专属性强，适用于吡仑帕奈中的2-(2-氧代-1-苯基-5-(N-氧化吡啶)-2-基-1,2-二氢吡啶-3-基)苯腈含量测定。

[关键词]LC-MS/MS；吡仑帕奈；遗传毒性杂质；分析方法

[Abstract] Objective To establish a high-performance liquid chromatography-mass spectrometry (LC-MS/MS) method for the determination of the genotoxic impurity 2-(2-oxo-1-phenyl-5-(N-pyridine oxide)-2-yl-1,2-dihydropyridine-3-yl)benzonitrile in perampanel. Methods The chromatographic conditions were as follows: a C₁₈ column (YMC-Triart C₁₈, 2.1*100 mm, 1.9 μm) using 0.05% formic acid aqueous solution ( mobile phase A) and acetonitrile (mobile phase B) in gradient elution (0~1 min, 10%B; 8~10 min, 90%B; 10.1~12 min, 10%B). The flow rate was 0.3 ml/min, injection volume was 5μl. The mass spectrometry conditions were as follows: electro spray ionization source (ESI⁺), multistage reaction monitoring (MRM) mode, ion spray voltage of 5500 V, ion source gas pressure of 50 psi, curtain gas pressure of 50 psi, auxiliary heating gas pressure of 50 psi, drying gas temperature is 500 ℃, carrier gas flow of 500 L/h, declustering potential of 150 V, collision energy of 27 V, monitoring ion pair of 366.0→273.0 and scanning time of 100 ms. The 0~6.8 min HPLC eluent was entered into the mass spectrometry for detection, and the 6.8~12 min HPLC eluent was cut into the waste. Results 2-(2-oxo-1-phenyl-5-(N-oxidepyridine)-2-yl-1,2-dihydropyridine-3-yl)benzonitrile had good linearity in the range of 3.76~18.80 ng/ml (r=0.9989), the limits of detection and quantification were 1.13 ng/ml and 3.38 ng/ml, respectively, and the recovery rate was 85.9%~94.2%, with good stability. It has strong specificity and is suitable for the determination of 2-(2-oxo-1-phenyl-5-(N-oxopyridine)-2-yl-1,2-dihydropyridine-3-yl) benzonitrile content in perampanel.

[Keyword] LC-MS/MS, Perampanel, genotoxic impurities, analytical methods

订阅方式：
①在线订阅（推荐）：www.sdchem.net.cn
②邮局订阅：邮发代号24-109

投稿方式：
①在线投稿（推荐）：www.sdchem.net.cn
　　作者只需要简单注册获得用户名和密码后，就可随时进行投稿、查稿，全程跟踪稿件的发表过程，使您的论文发表更加方便、快捷、透明、高效。
②邮箱投稿：sdhgtg@163.com sdhg@sdchem.net
　　若“在线投稿”不成功，可使用邮箱投稿，投稿邮件主题：第一作者名字/稿件题目。
投稿时请注意以下事项：
　　①文前应有中英文“题目”、“作者姓名”、“单位”、“邮编”、“摘要”、“关键词”；
　　②作者简介包括：姓名、出生年、性别、民族、籍贯或出生地、工作单位、职务或职称、学位、研究方向；
　　③论文末应附“参考文献”，执行国标GB/T7714-2005标准，“参考文献”序号应与论文中出现的顺序相符；
　　④注明作者的联系方式，包括电话、E-mail、详细的通讯地址、邮编，以便联系并邮寄杂志。
　　 　                                                                                   山东化工稿件修改细则