摘要
建立了重要医药中间体2-羟基-3-甲氧基-3,3-二苯基丙酸对映体的高效液相色谱分离方法。采用手性色谱柱在正相条件下直接拆分2-羟基-3-甲氧基-3,3-二苯基丙酸对映体,考察了固定相种类、流动相中异丙醇比例、柱温、流速等对2-羟基-3-甲氧基-3,3-二苯基丙酸对映体分离的影响。最终确定其拆分条件为:色谱柱为Chiralpak ID(250 mm×4.6 mm,5.0μm),流动相为正己烷-异丙醇-三氟乙酸(97∶3∶0.1,v/v/v),流速为1.0 mL/min,检测波长为220 nm,柱温为25℃;在此条件下2-羟基-3-甲氧基-3,3-二苯基丙酸对映体的分离度为2.3。R构型的检测限、定量限分别为0.5μg/mL,1.0μg/mL,其在1～100μg/mL内线性关系良好(r=0.999 6)。平均回收率为98.4%～104.5%,峰面积的相对标准偏差为1.5%。3批中间体样品中R构型杂质含量均在合格范围内。所建立的分析方法简单快速,重现性好,可用于(S)-2-羟基-3-甲氧基-3,3-二苯基丙酸的异构体检测。
A high performance liquid chromatography method was established for the enantiomeric separation of important medicine intermediate 2-hydroxy-3-methoxy-3,3-diphenylpropionic acid.Baseline separation of 2-hydroxy-3-methoxy-3,3-diphenylpropionic acid was achieved under normal phase chromatographic mode using the chiral stationary phase.Effects of the types of chiral stationary phase,isopropanol modifier concentration,column temperature and flow rate were investigated.Ultimately,the optimized chromatographic conditions were as follows：the chromatographic column was Chiralpak ID（250 mm×4.6 mm,5 μm）,the mobile phase were hexane-isopropanol-trifluoroacetic acid（97 ∶ 3 ∶ 0.1,v/v/v）,the flow rate was 1.0 mL/min,the detection wavelength was 220 nm,the column temperature was 25 ℃.Under this condition,the resolution of 2-hydroxy-3-methoxy-3,3-diphenylpropionic acid enantiomer was 2.3.The detection limit and quantity limit of R-impurity were 0.5 μg/mL,1.0 μg/mL,respectively.It was good linear（r=0.999 6） over the range of 1～100 μg/mL.The average recoveries of standard addition of R-impurity were 98.4%～104.5%,and the related standard deviations of peak areas was 1.5%.R-impurity in the three batches of 2-hydroxy-3-methoxy-3,3-diphenylpropionic acid were in line with the requirements.The method using for detection of（S）-2-hydroxy-3-methoxy-3,3-diphenylpropionic acid isomer is simple,rapid and reproducible.
出处
《应用化工》
CAS
CSCD
2013年第8期1544-1547,共4页
Applied Chemical Industry
