手性固定相色谱法直接拆分曲美布汀、拉呋替丁和昂丹司琼对映异构体

Enantiomeric separation of trimebutine,lafutidine and ondansetron by HPLC using chiral stationary phase

目的:建立直接拆分3种消化系统用药曲美布汀、拉呋替丁和昂丹司琼对映体的液相色谱方法。方法:采用以万古霉素为手性固定相的Chirobiotic V2(250mm×4.6mm,5μm)色谱柱,在流速均为1.0mL·min^(-1),柱温均为20℃时,分离曲美布汀对映体、拉呋替丁对映体和昂丹司琼对映体的流动相分别为:甲醇-冰醋酸-三乙胺(100:0.075:0.025)、甲醇-冰醋酸-三乙胺(100:0.025:0.075)和20mmol·L^(-1)醋酸铵缓冲液(pH 4.5)-甲醇(50:50)。采用以α_1-酸糖蛋白手性固定相的Chiral-AGP(150mm×4.6mm,5μm)色谱柱,分离昂丹司琼对映体的色谱条件为:20mmol·L^(-1)醋酸铵缓冲液(pH 4.5)-乙腈(99.8:0.2)为流动相,流速为0.9mL·min^(-1),柱温为15℃。采用以卵类粘蛋白手性固定相的Ultron ES-OVM(150mm×4.6mm,5μm)色谱柱,分离昂丹司琼对映体的色谱条件为:乙腈-水-冰醋酸(2.5:97.5:0.0025)为流动相,流速为0.5 mL·min^(-1),柱温为20℃。结果:曲美布汀和拉呋替丁对映体在万古霉素手性固定相上能够完全分离,分离度分别为2.75和3.58;昂丹司琼对映体在万古霉素手性固定相上分离较差,分离度为0.61,但在α_1-酸糖蛋白手性固定相上分离较好,分离度为1.26,在卵类粘蛋白手性固定相上完全分离,分离度为1.50。结论:万古霉素手性固定相可以用于曲美布汀和拉呋替丁对映体的手性分离,卵类粘蛋白手性固定相可以用于昂丹司琼对映体的手性分离。

Objective：To develop chiral separation methods for the enantiomers of trimebutine,lafutidine and ondansetron. Method：Trimebutine ,lafutidine and ondansetron enantiomers were separated on vancomycin chiral stationary phase Chirobiotic V2（250 mm ×4. 6 mm,5 μm）at a flow rate 1.0 mL· min-lat 20℃ ,chromatographic conditions were mobile phases consisted of methanol- glacial acetic acid- triethylamine （100： 0. 075： 0. 025 ） ,methanol- glacial acetic acid - triethylamine （ 100： 0. 025： 0. 075 ） and 20 mmol·L ^-1 ammonium acetate （ pH 4. 5 ） - methanol （50： 50）for separation of trimebutine enantiomers,lafutidine enantiomers and ondansetron enantiomers ,respectively. Ondansetron en- antiomers were separated on eq acid glycoprotein chiral stationary phase Chiral - AGP （ 150 mm × 4. 6 mm, 5μm ）, and chromatographic conditions were a mobile phase consisted of 20 mmol·L^-1 ammonium acetate （pH 4. 5 ） - acetonitrile（99. 8： 0. 2）at a flow rate 0. 9 mL·min^-1 at 15℃. Ondansetron enantiomers were separated on an ovomucoid chiral stationary phase Ultron ES - OVM （150 mm × 4.6 mm, 5μm）and chromatographic conditions were a mobile phase consisted of acetonitrile -water glacial acetic acid （2. 5： 97.5： 0. 0025 ） at a flow rate 0. 5 mL·min^-1 at 20℃. Results： Trimebutine, lafutidine and ondansetron enantiomers were separated on vancomycin chiral stationary phase and the resolutions were 2.75,3.58 and 0. 61, respectively. Ondansetron enantiomers were separated on α1- acid glycoprotein chiral chiral stationary phase with resolution of separated on vancomycin chiral stationary chiral stationary phase. stationary phase and the resolution was 1.26, but separated on ovomucoid 1.50. Conclusion： Trimebutine and lafutidine enantiomers can be full separated on vancomycin chiral stationary phase and ondansetron enantiomers can be full separated on ovomucoid chiral stationary phase.