Strege M A
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285.
Anal Chem. 1998 Jul 1;70(13):2439-45. doi: 10.1021/ac9802271.
For the drug discovery efforts currently taking place within the pharmaceutical industry, natural product extracts have been found to provide a valuable source of molecular diversity which is complementary to that provided by traditional synthetic organic methods or combinatorial chemistry. However, there exists a need for analytical tools that can facilitate the separation and characterization of components from these sources in a rapid manner. Specifically, the evaluation of highly polar compounds (i.e., compounds that cannot be retained on traditional reversed-phase stationary phases) has been challenging, and a hydrophilic interaction chromatography-electrospray ionization mass spectrometry (HILIC-ESI-MS) method was developed to meet this need. In this investigation, amide-, Polyhydroxyethyl Aspartamide-, and cyclodextrin-based packings provided superior performance for the analysis of a set of polar natural product compounds. The properties of the mobile-phase buffers also greatly impacted the separations, and relative to other volatile buffering agents, ammonium acetate at a concentration of approximately 6.5 mM was determined to facilitate optimal HILIC retention, reproducibility, and durability. An optimized HILIC-ESI-MS system was successfully applied for the analysis of complex natural product mixtures. The techniques described in this report should also prove useful for the analysis of polar compounds from synthetic sources of molecular diversity such as combinatorial chemistry.
对于制药行业目前正在进行的药物研发工作而言，已发现天然产物提取物可提供有价值的分子多样性来源，这与传统合成有机方法或组合化学所提供的分子多样性互补。然而，需要有能够快速促进从这些来源分离和表征成分的分析工具。具体而言，对高极性化合物（即无法保留在传统反相固定相上的化合物）的评估一直具有挑战性，因此开发了一种亲水作用色谱 - 电喷雾电离质谱（HILIC - ESI - MS）方法来满足这一需求。在本研究中，基于酰胺、聚羟乙基天冬酰胺和环糊精的填料在分析一组极性天然产物化合物时表现出卓越的性能。流动相缓冲液的性质也对分离有很大影响，相对于其他挥发性缓冲剂，浓度约为6.5 mM的乙酸铵被确定有助于实现最佳的亲水作用色谱保留、重现性和耐用性。一个优化的HILIC - ESI - MS系统成功应用于复杂天然产物混合物的分析。本报告中描述的技术对于分析来自组合化学等合成分子多样性来源的极性化合物也应是有用的。
