色谱

色谱 ›› 2014, Vol. 32 ›› Issue (9): 1013-1018.DOI: 10.3724/SP.J.1123.2014.06026

• 研究论文 • 上一篇    下一篇

纤维素-三（4-甲基苯甲酸酯）手性固定相拆分5种芳基丙酸类药物对映体及其制剂的含量测定

罗安, 万强, 范华均, 陈智, 吴学昊, 黄晓文, 臧林泉   

  1. 广东药学院药科学院, 广东 广州 510006
  • 收稿日期:2014-06-17 修回日期:2014-07-14 出版日期:2014-09-08 发布日期:2014-08-30
  • 通讯作者: 范华均
  • 作者简介:范华均，junhuafan@126.com.
  • 基金资助:

    国家“重大新药创制”科技重大专项（2011ZX09102-001-31）；广东药学院师资队伍建设基金项目（52104109）.

Chiral separation of five arylpropionic acid drugs and determination of their enantiomers in pharmaceutical preparations by reversed-phase high performance liquid chromatography with cellulose-tris- (4-methylbenzoate) stationary phase

LUO An, WAN Qiang, FAN Huajun, CHEN Zhi, WU Xuehao, HUANG Xiaowen, ZANG Linquan   

  1. College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
  • Received:2014-06-17 Revised:2014-07-14 Online:2014-09-08 Published:2014-08-30

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摘要：

采用纤维素-三（4-甲基苯甲酸酯）（CTMB）手性固定相，利用反相色谱法研究了氟比洛芬、普拉洛芬、布洛芬、萘普生、洛索洛芬5种芳基丙酸类手性药物的色谱拆分行为。考察了流动相组成、酸碱添加剂及柱温对上述5种药物对映体分离的影响，并通过热力学研究及对映体结构分析对CTMB固定相的手性拆分机理进行了探讨。结果表明，除萘普生采用乙腈-0.1%（v/v）甲酸溶液外，以甲醇-0.1%（v/v）甲酸水溶液为流动相可使普拉洛芬、洛索洛芬、氟比洛芬和布洛芬的对映体间的分离度均大于1.5，CTMB固定相对这5种芳基丙酸类药物的手性拆分能力依次为普拉洛芬>洛索洛芬>氟比洛芬>布洛芬>萘普生。在各自的优化色谱条件下，将方法应用于上述5种药物制剂的含量测定，结果令人满意。

关键词: 反相高效液相色谱法, 芳基丙酸类药物, 手性拆分, 手性固定相, 纤维素-三（4-甲基苯甲酸酯）

Abstract:

Chromatographic behaviors for enantiomeric separation of arylpropionic acid drugs were systematically developed by reversed phase-high performance liquid chromatography (RP-HPLC) using cellulose-tris-(4-methylbenzoate) (CTMB) as chiral stationary phase (CSP). The effects of the composition of the mobile phase, additives and temperature on chiral separation of flurbiprofen, pranoprofen, naproxen, ibuprofen and loxoprofen were further investigated. The enantiomers had been successfully separated on CSP of CTMB by the mobile phase of methanol-0.1%(v/v) formic acid except naproxen by acetonitrile-0.1%(v/v) formic acid at 25 ℃. The mechanisms of the racemic resolution for the above mentioned five drugs are discussed thermodynamically and structurally. The resolutions between respective enantiomers for arylpropionic acid drugs on CTMB had significant differences due to their chromatographic behaviors. The order of resolutions ranked pranoprofen, loxoprofen, flurbiprofen, ibuprofen and naproxen. The method established has been successfully applied to the determination of the enantiomers of the five drugs in commercial preparations under the optimized conditions. It proved that the method is simple, reliable and accurate.

Key words: arylpropionic acid drugs, cellulose-tris-(4-methylbenzoate), chiral separation, chiral stationary phase, reversed-phase high performance liquid chromatography (RP-HPLC)

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