Egis Pharmaceuticals Plc. , Keresztúri út 30-38, 1106, Budapest, Hungary.
Budapest University of Technology and Economics, Department of Inorganic and Analytical Chemistry, Szt. Gellért tér 4, 1111, Budapest, Hungary.
J Pharm Biomed Anal. 2014 Feb;89:67-75. doi: 10.1016/j.jpba.2013.10.029. Epub 2013 Nov 1.
The goal of this study was to evaluate the accuracy of simulated robustness testing using commercial modelling software (DryLab) and state-of-the-art stationary phases. For this purpose, a mixture of amlodipine and its seven related impurities was analyzed on short narrow bore columns (50×2.1mm, packed with sub-2μm particles) providing short analysis times. The performance of commercial modelling software for robustness testing was systematically compared to experimental measurements and DoE based predictions. We have demonstrated that the reliability of predictions was good, since the predicted retention times and resolutions were in good agreement with the experimental ones at the edges of the design space. In average, the retention time relative errors were <1.0%, while the predicted critical resolution errors were comprised between 6.9 and 17.2%. Because the simulated robustness testing requires significantly less experimental work than the DoE based predictions, we think that robustness could now be investigated in the early stage of method development. Moreover, the column interchangeability, which is also an important part of robustness testing, was investigated considering five different C8 and C18 columns packed with sub-2μm particles. Again, thanks to modelling software, we proved that the separation was feasible on all columns within the same analysis time (less than 4min), by proper adjustments of variables.
本研究的目的是评估使用商业建模软件（DryLab）和最先进的固定相进行模拟稳健性测试的准确性。为此，在短窄径柱（50×2.1mm，填充亚 2μm 颗粒）上分析了氨氯地平和其七种相关杂质的混合物，以实现短的分析时间。商业建模软件用于稳健性测试的性能与实验测量和基于 DoE 的预测进行了系统比较。我们已经证明，预测的可靠性良好，因为在设计空间的边缘，预测的保留时间和分辨率与实验值吻合良好。平均而言，保留时间的相对误差<1.0%，而预测的关键分辨率误差在 6.9%至 17.2%之间。由于模拟稳健性测试比基于 DoE 的预测需要少得多的实验工作，因此我们认为现在可以在方法开发的早期阶段研究稳健性。此外，还考虑了填充亚 2μm 颗粒的五个不同 C8 和 C18 柱，对柱可互换性（也是稳健性测试的重要部分）进行了研究。同样，由于建模软件，我们证明了通过适当调整变量，在相同的分析时间（不到 4 分钟）内，可以在所有柱上实现分离。
