反相高效液相色谱法拆分醋酸棉酚对映异构体

RP-HPLC chiral separation of gossypol acetic acid

目的建立醋酸棉酚的手性分析方法,用于拆分产物光学纯度的测定。方法采用高效液相色谱法,色谱柱为Chiralcel OD-RH手性柱(150 mm×4.6 mm,5μm),流动相为pH3.5磷酸三乙胺缓冲溶液-乙腈(体积比30∶70),流速为1.0 mL/min;检测波长为225 nm。结果醋酸棉酚消旋体在此条件下分离度为5.3。该方法用于手性拆分得到的光学对映体的光学纯度测定,对映体过量百分比(ee)在98%以上。结论本方法分离度、精密度和稳定性好,可用于一类抗肿瘤新药左旋(-)-醋酸棉酚原料药的合成反应监测、有关物质检测,及相关制剂的定量分析、有关物质检测,结果准确可靠。

Objective To establish an HPLC method for chiral separation of gossypol acetic acid enantiomers,and to determine the optical purity of the product.Methods RP-HPLC with Chiralcel OD-RH chiral column was adopted.The mobile phase was triethylamine phosphate buffer solution-acetonitrile（30∶70） with pH 3.5 at the flow rate of 1.0 mL/min,and the detective wavelength was 225 nm.Results The resolution of gossypol acetic acid enantiomers was 5.3 under the above conditions.The method was used for determining the optical purity of the separated products.The enantiomeric excess percentage（ee） was over 98%.Conclusion With good resolution,precision and repeatability,the method can be used for monitoring the synthesis reaction of（l）-（-）-gossypol acetic acid,which is a new anti-tumor drug of the first class,the detection of related substances and quantitative analysis of its preparations.