Bui Hai, Masquelin Thierry, Perun Tom, Castle Tom, Dage Jeff, Kuo Ming-Shang
Lilly Research Laboratories, Indianapolis, IN 46285, USA.
J Chromatogr A. 2008 Oct 10;1206(2):186-95. doi: 10.1016/j.chroma.2008.08.050. Epub 2008 Aug 20.
In this study, the retention behaviors of pharmaceutical and drug-like compounds in supercritical fluid chromatography (SFC) with polar stationary phases were evaluated using linear solvation energy relationships (LSERs). We used more than 200 compounds, including mono-, di-substituted benzenes, and other marketed drugs with a wide range of solvation descriptors. The dominant contribution to positive retention was the hydrogen bond donor acidity of the solutes, particularly for pyridine and amino columns. That factor is determined by the difference in basicity between the mobile and stationary phases. Another significant contributor to retention behavior was the hydrogen bond acceptor basicity of the solutes made particularly for diol and amino columns. The hydrogen bond donating ability is small for cyano and pyridine stationary phases (or should be zero) since those two phases lack hydrogen bond donor groups. The LSER results showed that the SFC retention behavior of compounds using carbon dioxide-methanol with polar stationary phases was close to that reported for normal phase LC using hexane-methanol. As expected, mobile phases containing high percentages of modifier resulted in decreased retention times for most compounds. A greater knowledge of the nature of solute/stationary phase and solute/mobile phase allows a more rapid and efficient choice in high-throughput screening of compound libraries.
在本研究中,采用线性溶剂化能关系(LSERs)评估了药物及类药物化合物在具有极性固定相的超临界流体色谱(SFC)中的保留行为。我们使用了200多种化合物,包括单取代和二取代苯以及其他具有广泛溶剂化描述符的市售药物。对正向保留起主要作用的是溶质的氢键供体酸度,特别是对于吡啶柱和氨基柱而言。该因素由流动相和固定相之间的碱度差异决定。保留行为的另一个重要贡献因素是溶质的氢键受体碱度,特别是对于二醇柱和氨基柱而言。对于氰基柱和吡啶固定相,氢键供体能力较小(或应为零),因为这两个固定相缺乏氢键供体基团。LSER结果表明,使用二氧化碳 - 甲醇与极性固定相时化合物的SFC保留行为与使用己烷 - 甲醇的正相液相色谱所报道的保留行为相近。正如预期的那样,含有高百分比改性剂的流动相导致大多数化合物的保留时间缩短。对溶质/固定相和溶质/流动相性质有更深入的了解有助于在化合物库的高通量筛选中做出更快速有效的选择。