联合使用反相液相色谱, 柱切换以及两性离子交换-反相亲水性相互作用混合模式色谱-质谱法分析抗生素中的杂质

doi:10.5246/jcps.2014.02.014

中国药学(英文版)

联合使用反相液相色谱, 柱切换以及两性离子交换-反相亲水性相互作用混合模式色谱-质谱法分析抗生素中的杂质

卢丽, 李进, 金少鸿, 胡昌勤^*

1. 中国食品药品检定研究院, 北京 100050
2. 江苏省食品药品检验所, 江苏南京 210008

收稿日期:2013-08-11 修回日期:2013-09-27 出版日期:2014-02-15 发布日期:2014-01-25
通讯作者: 胡昌勤*
作者简介:*Corresponding author. Tel.: +86-10-67095308; Fax: +86-10-65115148; E-mail: hucq@nifdc.org.cn
基金资助:
The Key Projects in the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (Grant No. 2012BAK25B02).

Combination of reversed phase liquid chromatography and zwitterion exchange-reversed phase-hydrophilic interaction mixed-mode liquid chromatography coupled with mass spectrometry for the analysis of antibiotics and their impurities

Li Lu, Jin Li, Shaohong Jin, Changqin Hu^*

1. National Institutes for Food and Drug Control, Beijing 100050, China
2. Jiangsu Institute for Food and Drug Control, Nanjing 210008, China

Received:2013-08-11 Revised:2013-09-27 Online:2014-02-15 Published:2014-01-25
Contact: Changqin Hu*
About author:*Corresponding author. Tel.: +86-10-67095308; Fax: +86-10-65115148; E-mail: hucq@nifdc.org.cn
Supported by:
The Key Projects in the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (Grant No. 2012BAK25B02).

摘要/Abstract

摘要：

建立并优化了一种二维柱切换、高效液相色谱-质谱联用(LC-MS/MS)系统, 用于分析抗生素及其有关物质。在一维色谱中, 采用两性离子交换-反相亲水性相互作用(ZIC-RP-HILIC)混合模式色谱柱对目标杂质进行分离, 并采用液质联用技术(LC-MS/MS)进行检测。在二维色谱中, 采用常规的反相LC色谱柱对供试品及其杂质进行分析。ZIC-RP-HILIC混合模式色谱系统的流动相为一种适用于LC-MS/MS的可挥发性缓冲盐, 能够提高杂质的离子化效率, 便于对目标杂质进行结构解析。直接采用ZIC-RP-HILIC-MS系统, 对使用离子对反相色谱分离的抗生素杂质进行定性分析。ZIC-RP-HILIC混合模式色谱与反相LC色谱系统之间的正交性, 进一步保证了杂质检测的全面性。此方法的优势体现在对青霉素V钾, 苯唑青霉素钠、头孢曲松钠的杂质分析中。另外, 该方法便于进行抗生素的杂质谱分析, 并可用于其它药物的杂质分析。

关键词: 杂质谱, 二维色谱, 柱切换, 混合模式色谱, 高效液相色谱/质谱联用

Abstract:

In this study, a system involving two-dimensional, column-switching high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry (LC-MS/MS) was developed and optimized for the analysis of antibiotics and their related substances. In the first-dimensional chromatography, the analytes were separated on a zwitterion exchange-reversed phase-hydrophilic interaction (ZIC-RP-HILIC) mixed-mode column coupled with tandem mass spectrometry (LC-MS/MS). A commonly used reversed phase LC column was employed in the second-dimensional chromatography. The mobile phase for the ZIC-RP-HILIC mixed-mode chromatography consisted of a volatile buffer that was compatible with LC-MS/MS, which enhanced the efficiency of ionization for structure elucidation. The antibiotic impurities eluted in the ion-pairing reversed phase chromatography were directly characterized by the ZIC-RP-HILIC-MS system, and the orthogonal separation of ZIC-RP-HILIC mixed-mode chromatography and reversed phase LC provided extra confidence that no impurity was missed. The efficiency of this method was demonstrated in the analysis of penicillin V potassium, oxacillin sodium, ceftriaxone sodium, and their impurities. In addition, this method is convenient for impurity profiling of antibiotics, and may be used for the analysis of other pharmaceutical ingredients.

Key words: Impurity profiling, Two-dimensional chromatography, Column-switching, Mixed-mode chromatography, LC/MSn

中图分类号:

R917

Supporting: The Key Projects in the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (Grant No. 2012BAK25B02).

卢丽, 李进, 金少鸿, 胡昌勤. 联合使用反相液相色谱, 柱切换以及两性离子交换-反相亲水性相互作用混合模式色谱-质谱法分析抗生素中的杂质[J]. 中国药学(英文版), DOI: 10.5246/jcps.2014.02.014.

Li Lu, Jin Li, Shaohong Jin, Changqin Hu. Combination of reversed phase liquid chromatography and zwitterion exchange-reversed phase-hydrophilic interaction mixed-mode liquid chromatography coupled with mass spectrometry for the analysis of antibiotics and their impurities[J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2014.02.014.

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联合使用反相液相色谱, 柱切换以及两性离子交换-反相亲水性相互作用混合模式色谱-质谱法分析抗生素中的杂质

Combination of reversed phase liquid chromatography and zwitterion exchange-reversed phase-hydrophilic interaction mixed-mode liquid chromatography coupled with mass spectrometry for the analysis of antibiotics and their impurities

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