Li Huajun, Chen Qian
Zhejiang Starry Pharmaceutical Co. Ltd., Taizhou 317300, China.
Se Pu. 2018 Oct 8;36(10):1061-1066. doi: 10.3724/SP.J.1123.2018.06001.
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.
基于制备型高效液相色谱法（prep-HPLC）对高纯度碘帕醇的分离纯化方法进行了开发与优化。在本研究中，首先建立了用于分析碘帕醇的反相分离方法。考察了色谱参数，包括两种键合量不同的固定相、柱温以及进样量，对碘帕醇保留时间、分离度和峰形的影响。结果表明，在键合量为13.7%的C18-1柱（250 mm×4.6 mm，10 μm）上碘帕醇实现了良好的保留和分离度。碘帕醇的保留随柱温升高而减弱，导致碘帕醇与杂质之间的分离度降低。因此，将柱温调整为20 - 30℃。同时，进样量增加也不利于碘帕醇的保留或杂质的去除。在C18-1柱（270 mm×50 mm，10 μm）上，以水 - 甲醇为流动相，在20℃柱温下进行制备型高效液相色谱分离。制备后，碘帕醇样品的色谱纯度为98.97%，回收率为93.44%，其有关物质均符合限度要求。该方法能有效降低杂质水平，回收率高，有助于碘帕醇分离纯化的研究。
