Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
J Pharm Biomed Anal. 2011 Sep 10;56(2):280-92. doi: 10.1016/j.jpba.2011.05.028. Epub 2011 May 20.
A strategy for developing chromatographic methods designed to determine impurities and degradation products in active pharmaceutical ingredients and drug products is presented. Selectivity is achieved by evaluating a chromatographic space comprised of 12 stationary/mobile phase combinations. Stationary phases predicted to be orthogonal based on their hydrophobic subtraction model parameters used. The particle sizes, column dimensions, and gradient times chosen provide high peak capacities and allow operation at backpressures that can be achieved with standard instrumentation. The mobile phases utilized are compatible with MS detection and cover a wide range of pH, solvent strength, and solvent selectivity. Analyte detection is accomplished using a combination of diode array and mass spectroscopic detectors which allow mixtures of project compounds to be injected and selectively detected. Automation of data acquisition and processing is accomplished using AutoChrom software from ACD\Labs. The strategy is illustrated with detailed data from two case studies and summary data from nineteen pharmaceutical projects.
介绍了一种用于开发旨在确定原料药和药物产品中杂质和降解产物的色谱方法的策略。通过评估由 12 种固定相/流动相组合组成的色谱空间来实现选择性。根据其疏水扣除模型参数预测的固定相是正交的。选择的粒径、柱尺寸和梯度时间提供了高的峰容量，并允许在可与标准仪器达到的背压下操作。所用的流动相与 MS 检测兼容，并涵盖了广泛的 pH 值、溶剂强度和溶剂选择性。使用二极管阵列和质谱检测器的组合来完成分析物的检测，这允许项目化合物的混合物被注入并选择性地检测。使用 ACD\Labs 的 AutoChrom 软件实现数据采集和处理的自动化。该策略通过两个案例研究的详细数据和十九个药物项目的汇总数据进行了说明。
