生长抑素二聚体杂质的制备方法研究

Study on Preparation and Technology of Somatostain Dimer Impurity

目的开发一种工艺简单可连续生产制备纯化生长抑素二聚体的方法。方法本文以生长抑素为例,介绍一种二聚体的制备方法,向生长抑素溶液中加入碱溶液调节pH值,室温搅拌,再加入酸溶液调节pH值,加水稀释得进样溶液,经制备柱纯化和冻干后得生长抑素二聚体纯品。结果获得生长抑素对称性二聚体纯度99.63%,生长抑素不对称性二聚体纯度99.22%,两种二聚体总收率为53.0%。结论本工艺效率高、纯度高,采用梯度洗脱,节约溶剂,色谱系统运行时间短、可有效分离获得生长抑素对称性二聚体和生长抑素不对称性二聚体,且可以连续进样制备纯化,制备流动相未使用离子对试剂,填料使用寿命长,具有良好的应用前景。

OBJECTIVE To develop a simple and continuous method for production and purification of somatostatin dime.METHODS Taking somatostatin as an example,this paper introduced a preparation method of dimer.The pH value of somatostatin solution was adjusted by adding alkali solution at room temperature.Then the somatostatin solution was added acid solution to adjust the pH value,and diluted with water to obtain the injection solution.After the preparation by column purification and lyophilization,somatostatin dimer was obtained.RESULTS The purity of the somatostatin symmetrical dimers was 99.63%.The purity of the somatostatin asymmetric dimer was 99.22%,and the total yield of the two dimers was 53.0%.CONCLUSION This process has high efficiency and high purity,by using the gradient elution,saves solvent and has a short chromatographic running time1is short,which can effectively and continuously separate somatostatin symmetrical dimers and somatostatin asymmetry dimers without preparing ion-pair mobile phase reagent.The column filler has a long service life and the method has good application prospects.