Zizkovský Václav, Kucera Radim, Klimes Jirí, Dohnal Jirí
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
J Chromatogr A. 2008 May 2;1189(1-2):83-91. doi: 10.1016/j.chroma.2007.12.017. Epub 2007 Dec 15.
Improvements in stationary phase stability have been and remain a great task for research of new stationary phases. Metal oxide-based stationary phases appear as one of perspective alternatives to classical silica based stationary phases regarding to their similar effectiveness, different selectivity, different retention mechanism and mainly better chemical and thermal stability. In this study, the retention behaviour of ondansetron and its five pharmacopoeial impurities on TiO(2)-based reversed phase was investigated. The influence of buffer type, pH and concentration on retention was studied. Different types and amount of organic solvent in mobile phase were tested. The effect of temperature and flow rate on separation was investigated. The separation conditions were optimized and developed method validated. The retention parameters - retention time (t(R)), retention factor (k'), theoretical plate number (N), resolution between peaks due to nearby peaks (R(s)) and symmetry factor (A(s)) have been compared to parameters achieved on polybutadiene-coated zirconia column. The thermodynamic parameters of retention of analysed compounds - enthalpy, entropy and Gibbs free energy - were calculated and compared to those achieved on polybutadiene-coated zirconia column. This work proves similarity of retention behaviour of ondansetron and its five related compounds on zirconia-based and titania-based stationary phases and potential utilisation of polyethylene covered TiO(2)-based reversed stationary phase as an alternative to polybutadiene-coated ZrO(2) stationary phase in pharmaceutical analysis of ondansetron.
固定相稳定性的改善一直是并且仍然是新型固定相研究的一项重大任务。基于金属氧化物的固定相，由于其类似的有效性、不同的选择性、不同的保留机制以及主要更好的化学和热稳定性，似乎是传统硅胶基固定相的一种有前景的替代物。在本研究中，考察了昂丹司琼及其五个药典杂质在TiO₂ 基反相柱上的保留行为。研究了缓冲液类型、pH值和浓度对保留的影响。测试了流动相中不同类型和量的有机溶剂。考察了温度和流速对分离的影响。对分离条件进行了优化，并对所建立的方法进行了验证。将保留参数——保留时间（t(R)）、保留因子（k'）、理论塔板数（N）、相邻峰之间的峰分辨率（R(s)）和对称因子（A(s)）与在聚丁二烯涂覆的氧化锆柱上获得的参数进行了比较。计算了分析化合物保留的热力学参数——焓、熵和吉布斯自由能，并与在聚丁二烯涂覆的氧化锆柱上获得的参数进行了比较。这项工作证明了昂丹司琼及其五个相关化合物在氧化锆基和二氧化钛基固定相上保留行为的相似性，以及在昂丹司琼的药物分析中，聚乙烯覆盖的TiO₂ 基反相固定相作为聚丁二烯涂覆的ZrO₂ 固定相替代品的潜在用途。
