Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
J Pharm Biomed Anal. 2012 Mar 5;61:176-83. doi: 10.1016/j.jpba.2011.11.030. Epub 2011 Dec 6.
Knowledge of drug diffusivity is of key importance in the understanding of a number of pharmaceutical and biological processes. However, experimentally determined diffusion coefficients and hydrodynamic radii are only reported for a limited number of drug substances. In this work, Taylor dispersion analysis conducted using capillary electrophoresis instrumentation coupled with a UV imaging detector, with two detection windows along the capillary, is introduced as a powerful method for the determination of drug diffusivities in nanoliter samples. Several potential advantages associated with applying two detection windows instead of one window as done in most previous studies were identified. Overall diffusion coefficient measurements performed using two detection windows are more robust and correction for changes in flow rate and sample volume is not required. The experimental conditions applied were suboptimal for performing single detection window measurements due to the relatively large sample volumes and may be optimized to alleviate the need for tedious correction procedures for this setup. The diffusivities of eleven aromatic compounds in water at 25 °C were determined, and showed a good agreement with the literature values. Furthermore, the diffusivities and hydrodynamic radii of four selected drug substances were determined in acetonitrile, methanol, isopropyl myristate, medium chain triglyceride, and propylene glycol in addition to water. The solvent viscosity was determined simultaneously along with the measurement of analyte diffusivity. Drug diffusivities decreased with increasing solvent viscosity. Taylor dispersion analysis is a robust, simple and automated method of quantification of diffusion coefficients even in media with a relatively higher viscosity than water.
药物扩散系数的知识对于理解许多药物和生物学过程至关重要。然而，实验确定的扩散系数和流体力学半径仅报告了有限数量的药物物质。在这项工作中，使用毛细管电泳仪器结合紫外成像检测器进行的泰勒分散分析被引入作为一种强大的方法，用于在纳升级样品中测定药物的扩散系数。确定了与大多数先前研究中使用一个检测窗口相比，应用两个检测窗口的一些潜在优势。使用两个检测窗口进行的总体扩散系数测量更稳健，不需要校正流速和样品体积的变化。由于相对较大的样品体积，应用的实验条件对于执行单检测窗口测量不是最佳的，并且可以进行优化以减轻对于这种设置繁琐的校正程序的需求。在 25°C 下测定了十一种芳香族化合物在水中的扩散系数，并且与文献值吻合良好。此外，还在乙腈、甲醇、肉豆蔻异丙酯、中链甘油三酯和丙二醇以及水中测定了四种选定药物物质的扩散系数和流体力学半径。同时测定了溶剂粘度以及分析物的扩散系数。药物扩散系数随着溶剂粘度的增加而降低。泰勒分散分析是一种强大、简单且自动的定量扩散系数的方法，即使在比水具有相对更高粘度的介质中也是如此。
