β-环糊精类手性液相色谱固定相拆分和测定药片中美托洛尔对映体

Enantioseparation and determination of metoprolol enantiomers in tablets on a β-cyclodextrin-based chiral stationary phase by HPLC

采用新型的硝基苯胺衍生化β-环糊精键合有序介孔SBA-15液相色谱手性固定相（NCDSP）,在极性有机模式下实现了美托洛尔对映体的快速拆分。优化了流动相中甲醇含量、冰乙酸、三乙胺的比例和含量,并研究了温度对分离的影响。实验表明优化的色谱条件为：乙腈/甲醇/冰乙酸/三乙胺体积比95/5/1.5/1.5,流速为0.5 mL/min,柱温为20℃,检测波长为275 nm。在该条件下,美托洛尔对映体的离度为1.80,拆分时间较短（〈15 min）。在此基础上建立了酒石酸美托洛尔药片中对映体含量的快速测定方法,两对映体的浓度在2.2-140μg/mL范围内呈良好的线性关系（r=0.9993~0.9996）,平均回收率为97.6%-103.4%,检出限为0.2μg/mL,两对映体测定结果的日内和日间RSD分别小于1.4%和1.9%（n=5）。

In this paper, a novel nitrophenylamino- β-cyclodextrin-bonded ordered mesoporous SBA- 15 stationary phase （NCDSP） for HPLC was prepared. The fast enantioseparation of metoprolol enantiomers on the new stationary phase was achieved in polar organic solvent mode. Some chromatographic conditions, such as the methanol content, the proportion and contents of glcial acetic acid/triethylamine in mobile phase and column temperature were optimized in order to maxmize the resolution. The results showed that the optimal condition was as follows： the volumic ration of acetonitrile /methanol/glacial acetic acid/triethylamine in mobile phase was 95/5/1.5/1.5 at a flow rate of 0. 5 mL/min. The column temperature was 20 ℃. The detection wavelength was 275 nm. The resolution of metoprolol enantiomers reached up to 1.80. The analysis time was rather short within 15 min under the above conditions. Based on the optimization, a fast quantitative method of metoprolol tart.rate enantiomers in tablets was established. The good linear relationships were observed in the range of 2.2 - 140 μg/mL for both enantiomers （r = 0. 9993 - 0. 9996 ）. The average recoveries of two enantiomers were 97.6% - 103.4% with RSDs of intra-day （ 〈 1.4% ） and inter-day （ 〈 1.9%, n = 5 ）, respectively. The detection limits of metoprolol enantiomers were 0. 2 μg/mL.