HPLC法分析奈必洛尔中间体及其3种非对映异构体

Determination of the Intermediate of Nebivolol and Its Three Diastereomers by HPLC

建立了HPLC法分析奈必洛尔中间体的3种非对映异构体。采用HypersilTM ODS C18柱,以甲醇和水为流动相,梯度洗脱,检测波长为243 nm。结果显示,该色谱条件下,奈必洛尔中间体(R)-1-[(R)-6-氟色满-2-基]-2-[(R)-对甲苯基-甲基-亚磺酰基]乙醇及其3种非对映异构体杂质[(SRR)-、(RSR)-和(SSR)-构型]可有效分离。该中间体及其3种非对映异构体均在0.2~10μg/ml内线性关系良好,3种非对映异构体杂质的检测限分别为10.11、10.22、10.22 ng/ml,定量限分别为30.33、30.64、30.64 ng/ml。加样回收率为95.6%~102.2%,RSD(n=9)为1.33%~1.74%。本法专属性较好,准确度较高,可为奈必洛尔的不对称全合成过程控制提供参考。

An HPLC method was established for determination of three diastereomers in an intermediate of nebivolol,named(R)-1-[(R)-6-fluorochroman-2-yl]-2-[(R)-p-tolyl-methyl-sulfinyl]ethanol.A Hypersil?ODS C18 column was used to separate the(RRR)configuration of intermediate and its three diastereomers with mobile phase composed of methanol and water in a gradient elution mode.The detection wavelength was 243 nm.It was linear for the intermediate and its three diastereomers[(SRR)-,(RSR)-and(SSR)-diastereomers]in the range of 0.2-10μg/ml.The detection limits of the three diastereomers were respectively 10.11,10.22,10.22 ng/ml,and the quantification limits were respectively 30.33,30.64,30.64 ng/ml.The sample recovery rates were 95.6%-102.2%,and the RSDs(n=9)were1.33%-1.74%.This method has good specificity and high accuracy,which provides some references for the control of the asymmetric synthesis of nebivolol.