色谱

色谱 ›› 2012, Vol. 30 ›› Issue (10): 1026-1030.DOI: 10.3724/SP.J.1123.2012.06022

• 研究论文 • 上一篇    下一篇

高效液相色谱-四极杆飞行时间质谱法快速鉴定硝苯地平原料药中杂质

朱培曦1, 丁丽霞2*, 何佳佳3, 郑国钢1*   

  1. 1. 浙江省食品药品检验研究院, 浙江 杭州 310004; 2. 中国食品药品检定研究院, 北京 100050；3. 浙江工业大学药学院, 浙江 杭州 310014
  • 收稿日期:2012-06-18 修回日期:2012-08-02 出版日期:2012-10-28 发布日期:2012-10-17
  • 通讯作者: 丁丽霞,硕士生导师,高级研究员,研究方向为药品检验及质量标准. E-mail： dinglx@nicpbp.org.cn.郑国刚,主任药师,研究方向为化学药品分析检验. Tel: (0571)86459413, E-mail: zgg0617@126.com.
  • 基金资助:

    科技部重大新药创制课题(2011ZX09303-001).

Rapid characterization of impurities in the bulk drug of nifedipine by high performance liquid chromatography-quadrupole time of fight mass spectrometry

ZHU Peixi1, DING Lixia2*, HE Jiajia3, ZHENG Guogang1*   

  1. 1. Zhejiang Institute for Food and Drug Control, Hangzhou 310004, China; 2. National Institute of Food and Drug Control, Beijing 100050, China; 3. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
  • Received:2012-06-18 Revised:2012-08-02 Online:2012-10-28 Published:2012-10-17

PDF

426

被引次数

4

摘要： 利用高效液相色谱-四极杆飞行时间质谱法(HPLC-QTOF MS)对硝苯地平原料药的4种杂质进行了在线的质谱分析。色谱柱为Kromasil C18(250 mm×4.6 mm, 5 μm),流动相为甲醇-水(60:40, v/v),检测波长为235 nm。通过紫外检测器和四极杆飞行时间质谱仪在线检测,分离并检测了硝苯地平及其杂质,获得了它们的紫外光谱和质谱数据;通过比较加合质子的硝苯地平和杂质的准分子离子的碎裂特征,直接推断出了3个杂质可能的结构,其中1个为未知杂质;采用与对照品保留时间和质谱数据的比对,确定了另外1个杂质的结构。实验表明,HPLC-QTOF MS可以快速鉴定硝苯地平中杂质的化学成分。

关键词: 高效液相色谱-四极杆飞行时间质谱, 鉴定, 硝苯地平, 原料药, 杂质

Abstract: Four impurities in the bulk drug of nifedipine were detected by means of high performance liquid chromatography coupled with quadrupole time of fight mass spectrometry (HPLC-QTOF MS). A Kromasil C18 HPLC column (250 mm×4.6 mm, 5 μm) was used with methanol-water (60:40, v/v) as mobile phase. The column temperature was maintained at 35 ℃ with an ultraviolet （UV） detection wavelength of 235 nm for analysis. The eluates were detected with a UV detector and a quadrupole time of fight mass spectrometer in positive mode. The sample was infused into the mass spectrometer from the HPLC system through a T-junction with a splitting ratio of 3:1. The ion source temperature was set at 320 ℃ and the electrospray ionization (ESI) needle voltage was always set at 4000 V. Nitrogen was used as the drying gas and nebulizer gas. The protonated molecular ions were selected for determining the structures, and their fragmentation pathways were deduced. Based on the fragmentation behavior of nifedipine, the structures of 3 impurities were identified and one of them was identified as 3-ethyl-5-methyl-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, which was an unknown impurity to the best of our knowledge. An other impurity was identified by the comparison of the retention time and tandem mass spectra with the standard substance. The four proposed structures were all confirmed by exact mass evidence. The results indicated that the described method can be effectively applied to perform the identifications in nifedipine and its impurities.

Key words: bulk drug, identification, impurity, nifedipine, high performance liquid chromatography-quadrupole time of fight mass spectrometry (HPLC-QTOF MS)

中图分类号: