制备液相色谱法分离纯化碘帕醇

基于制备液相色谱法，开发与优化了碘帕醇的分离纯化工艺，制备得到高纯度碘帕醇样品。实验首先在分析水平发展碘帕醇的反相分离方法，考察了两种不同键合量的反相C18固定相、柱温和上样量对碘帕醇的保留、分离度和峰形等的影响。结果表明，碘帕醇在键合量为13.7%的反相C18-1分析柱（250 mm×4.6 mm，10 μm）上保留较好，且可与杂质有效分离；柱温升高，碘帕醇保留变弱，和杂质之间的分离度降低，最终选用20~25℃作为分离纯化的温度；上样量增加，碘帕醇出峰时间提前，不利于前杂的去除。在制备水平上，以水和甲醇为洗脱剂，在20℃条件下使用装填C18-1固定相的制备柱（270 mm×50 mm，10 μm）对碘帕醇进行分离纯化，制备的碘帕醇样品的色谱纯度可达98.97%，回收率为93.44%，各项有关物质均符合限量规定。该方法可以在保证高回收率的条件下有效降低杂质水平，为碘帕醇分离纯化生产工艺的开发提供新方法。

Separation and purification of iopamidol using preparative high-performance liquid chromatography

The development and optimization of separation and purification methods for high-purity iopamidol were performed based on preparative high-performance liquid chromatography (prep-HPLC). In this study, a reversed-phase separation method for the analysis of iopamidol was developed first. The effects of chromatographic parameters, including two kinds of stationary phase with different bonded amounts, column temperature, and sample loading capacity, on the retention, resolution, and peak shape of iopamidol were investigated. The results showed that good retention and resolution of iopamidol were realized on a C18-1 column (250 mm×4.6 mm, 10 μm) of which the bonded amount was 13.7%. Retention of iopamidol was weakened with increasing column temperature, resulting in a low resolution between iopamidol and impurities. Thus, the column temperature was adjusted to 20-30℃. Meanwhile, the increasing of loading capacities was also detrimental to retention of iopamidol or removal of impurities. Prep-HPLC was performed on the C18-1 column (270 mm×50 mm, 10 μm) with the mobile phase of water-methanol at a column temperature of 20℃. After preparation, the chromatographic purity of the iopamidol sample was 98.97% with recovery of 93.44%, and its related substances all met limited requirements. This method can reduce the impurity level effectively with a high recovery rate, which is helpful for the development of separation and purification of iopamide.