School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Bd d'Yvoy 20, 1211 Geneva 4, Switzerland.
J Chromatogr A. 2012 Mar 9;1228:221-31. doi: 10.1016/j.chroma.2011.09.013. Epub 2011 Sep 12.
The commercial C18 columns packed with sub-3 μm shell particles were tested and compared to a reference UHPLC column, in terms of kinetic performance as well as selectivity, retention capability, peak shape and loading capacity. For this purpose, a set of pharmaceutically relevant molecules was selected, including acidic, neutral and basic drugs. Regarding kinetic performance, h(opt) values for the shell particles were found between 1.7 and 2, while the UHPLC column provided a value of approximately 2.5. However, this impressive performance should be considered with caution, particularly for the construction of kinetic plots since h(opt) values were sometimes related to the column dimensions, depending on the provider (h(opt) comprised between 1.8 and 2.6 for longer columns of 150 mm packed with shell particles). Despite the non-porous inner core of the shell particles representing between 25 and 36% of the particle, we demonstrated that the decrease in retention was on the maximum equal to 15% for Ascentis column while Acquity and Poroshell were strictly equivalent in terms of retention. Concerning loading capacity, it remains comparable to that of fully porous sub-2 μm particles and always more pronounced with 0.1% formic acid vs. phosphate buffer. The loading capacity of the different columns was found to be better correlated to the pore volume or surface coverage than the shell thickness. Experimentally, the most pronounced overloading was observed with the Poroshell. Finally, the selectivity and peak shape were evaluated using a mixture of basic and acidic drugs. It appears that results were very similar between sub-3 μm shell particles and fully porous sub-2-μm particles for our mixture of compounds, showing the ability to transfer existing methods to shell particles, with only limited adjustments. This study confirms the potential of columns packed with shell particles and demonstrates the interest of such column technology with pharmaceutical compounds.
商业用的 3μm 以下核壳颗粒填充 C18 柱进行了测试，并与参考 UHPLC 柱进行了比较，比较的项目包括动力学性能以及选择性、保留能力、峰形和载样量。为此，选择了一组具有药学相关性的分子，包括酸性、中性和碱性药物。在动力学性能方面，核壳颗粒的 h(opt)值在 1.7 到 2 之间，而 UHPLC 柱提供的值约为 2.5。然而，这种令人印象深刻的性能应该谨慎考虑，特别是在构建动力学图时，因为 h(opt)值有时与柱尺寸有关，具体取决于供应商（对于更长的 150mm 柱，h(opt)值在 1.8 到 2.6 之间，这些柱用核壳颗粒填充）。尽管核壳颗粒的无孔内核占颗粒的 25%到 36%之间，但我们证明，对于 Ascentis 柱，保留的降低最多为 15%，而 Acquity 和 Poroshell 在保留方面完全相同。关于载样量，它与完全多孔的 2μm 以下颗粒的载样量相当，并且使用 0.1%甲酸与磷酸盐缓冲液相比，载样量总是更显著。不同柱的载样量发现与孔体积或表面覆盖率比壳层厚度更好相关。实验中，Poroshell 柱的过载现象最为明显。最后，使用碱性和酸性药物混合物评估了选择性和峰形。结果表明，对于我们的化合物混合物，3μm 以下核壳颗粒和完全多孔的 2-μm 以下颗粒之间的结果非常相似，这表明能够将现有的方法转移到核壳颗粒上，只需进行有限的调整。这项研究证实了核壳颗粒填充柱的潜力，并展示了这种柱技术在药物化合物方面的应用前景。
