摘要
目的对纯度98.0%左右(HPLC)的市场产品奥利司他进行分离纯化,制备纯度99.50%以上、单一杂质在0.10%以下的高纯度奥利司他。方法采用反相制备高效液相色谱技术,选择C18填料,以甲醇-水(85:15,v/v)为流动相,收集的目标组分经浓缩、结晶得到高纯度的奥利司他。结果小试和放大制备的奥利司他,纯度达99.50%以上、单一杂质控制在0.10%以下。放大制备了10kg以上的高纯产品,并解决了放大过程中配套设备和产品稳定性等实际问题。结论常规分离技术难以去除的奥利司他原料药中的杂质,采用反相制备高效液相色谱技术可有效去除,此技术适合生产制备高质量高附加值的药物。
Objective To purify orlistat more than 99.50% and control any impurity not more than 0.10%. Methods Preparative reversed-phase high performance liquid chromatography （RP-HPLC） was used for the purification of the crude orlistat. The preparation was carried out on a C18 column and a mobile phase of methanol-water（85：15, v/v）. The operation conditions including the flow rate of the mobile phase, injection volume and detection wave length were selected. The high purity product was presented with the target fractions concentrated and crystallized. Results The resulted purity of the orlistat was up to 99.80% and its single impurities below 0.10%. Furthermore, the scale-up separation was performed by using a C18 column of 300mm internal diameter, some problems such as the supporting equipments and the orlistat degradation were resolved, and more than 10kg of the high purity olistat were obtained. Conclusions The results showed that RP-HPLC is an efficient technique to separate orlistat and its impurities which were difficult to be isolated using the conventional methods such as solvent extraction, silica gel and ion exchange.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2014年第3期210-213,共4页
Chinese Journal of Antibiotics
关键词
奥利司他
反相制备高效液相色谱
高纯度
放大
Orlistat
Preparative Reversed-phase High Performance Liquid Chromatography （RP-HPLC）
High purity
Scale-up
