色谱

色谱

• 技术与应用 • 上一篇    下一篇

纤维素衍生物手性固定相高效液相色谱法分离盐酸川丁特罗对映体

蒋敏燕1, 秦峰1, 熊志立1, 张上上1, 潘莉2, 李发美1*   

  1. 1. 沈阳药科大学药学院, 辽宁 沈阳 110016; 2. 沈阳药科大学制药工程学院, 辽宁 沈阳 110016
  • 收稿日期:2011-07-04 修回日期:2011-08-02 出版日期:2011-11-28 发布日期:2011-12-25
  • 通讯作者: 李发美,博士生导师,教授,研究方向为药物色谱分析和色谱-质谱分析. Tel: (024)23986289,
  • 基金资助:

    国家科技重大专项课题(No. ZX09102-108)

Enantiomeric separation of trantinterol hydrochloride by high performance liquid chromatography on cellulose derivative-based chiral stationary phase

JIANG Minyan1, QIN Feng1, XIONG Zhili1, ZHANG Shangshang1, PAN Li2, LI Famei1*   

  1. 1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; 2. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China
  • Received:2011-07-04 Revised:2011-08-02 Online:2011-11-28 Published:2011-12-25

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摘要： 以纤维素三-(3,5-二甲基苯基氨基甲酸酯)为手性固定相(Lux Cellulose-1),建立了在正相色谱条件下直接分离盐酸川丁特罗对映体的高效液相色谱法。考察了乙醇、异丙醇等有机改性剂,三氟乙酸、二乙胺等流动相添加剂和柱温对对映体分离的影响。结果显示,酸性和碱性添加剂对对映体分离的影响最为显著: 添加二乙胺时两对映体无分离趋势;添加三氟乙酸时对映体保留强,且分离趋势明显;而同时添加三氟乙酸和二乙胺则两对映体分离显著改善,分离度可达4.0。优化后的色谱条件: 色谱柱为Lux Cellulose-1手性柱(250 mm×4.6 mm, 5 μm),流动相为正庚烷-乙醇-三氟乙酸-二乙胺(88:12:0.3:0.05, v/v/v/v),流速为1.0 mL/min,紫外检测波长为246 nm,柱温为25 ℃。该方法简便,快速,可用于左旋盐酸川丁特罗原料中右旋异构体杂质的检查。

关键词: 对映体分离, 高效液相色谱, 纤维素衍生物手性固定相, 盐酸川丁特罗

Abstract: A high performance liquid chromatographic (HPLC) method using cellulose tris-(3,5-dimethylphenylcarbamate) as chiral stationary phase (Lux Cellulose-1) for the separation of trantinterol hydrochloride enantiomers was developed. The method was based on normal phase model with n-heptane as the basal solvent of mobile phase. The influences of organic modifiers, mobile phase additives and column temperature on the retention and separation of the enantiomers were examined and discussed. It was demonstrated that the mobile phase additives had a dominant effect on the enantiomeric separation. No separation was observed with the addition of diethylamine only in the mobile phase, while the retention was increased and the enatiomeric separation was observed with the addition of trifluoroacetic acid. When both trifluoroacetic acid and diethylamine were added into the mobile phase, the enantioseparation was significantly improved with a resolution up to 4.0. Ethanol and isopropanol were investigated as the organic modifiers, and ethanol offered a better enatiomeric resolution for trantinterol hydrochloride. In the examined temperature range between 15 ℃ and 35 ℃ both separation factor and resolution were decreased with the increase of the column temperature. The optimized chiral HPLC method for the separation of trantinterol hydrochloride enantiomers involved a Lux Cellulose-1 column (250 mm×4.6 mm, 5 μm), a mobile phase of n-heptane/ethanol/trifluoroacetic acid/diethylamine (88:12:0.3:0.05, v/v/v/v) at a flow rate of 1.0 mL/min, a detection at 246 nm and a column temperature of 25 ℃. The method is simple and rapid for the enantiomeric impurity determination of (~)-trantinterol hydrochloride bulk samples.

Key words: cellulose derivative-based chiral stationary phase, enantiomeric separation, trantinterol hydrochloride, high performance liquid chromatography (HPLC)