Gyllenhaal Olle, Stefansson Morgan
Analytical Development, Pharmaceutical and Analytical R & D, AstraZeneca R & D Mölndal, Mölndal, Sweden.
Chirality. 2005 May 15;17(5):257-65. doi: 10.1002/chir.20160.
Enantiomeric separations of four 2-substituted propionic acid drugs have been studied using packed-column supercritical fluid chromatography (SFC) with amylose tris(3,5-dimethylphenylcarbamate) coated on silica as support (Chiralpak AD). Under standard conditions (i.e., flow rate, 1.5 ml/min; column temperature, 30 degrees C; back-pressure, 150 bar), the order of elution could be reversed when the polar alcohol modifier methanol in carbon dioxide was replaced by 2-propanol for ibuprofen, ketoprofen, and naproxen. For flurbiprofen, with the highest selectivity factor, no reversal was observed, although selectivity was reduced significantly with higher alcohols. Naproxen and flurbiprofen were also investigated with 2-butanol and 2-pentanol. The former showed reversal of elution order but not the latter. For higher alcohol modifiers, including 2-propanol, the peak symmetry was poor but could be improved by addition of citric acid in the alcohol modifier. These results stress the importance to investigate enantiomer elution order during the development of enantioselective methods and when chromatographic conditions are optimized. Preliminary experiments with column temperatures over the range of -15 to 45 degrees C revealed that, in a few cases, reversal took place with a change in temperature only.
使用涂覆在硅胶上的直链淀粉三（3,5-二甲基苯基氨基甲酸酯）作为固定相（Chiralpak AD）的填充柱超临界流体色谱（SFC），研究了四种2-取代丙酸类药物的对映体分离。在标准条件下（即流速1.5 ml/min；柱温30℃；背压150 bar），对于布洛芬、酮洛芬和萘普生，当二氧化碳中的极性醇改性剂甲醇被2-丙醇取代时，洗脱顺序可能会颠倒。对于选择性因子最高的氟比洛芬，虽然使用高级醇时选择性显著降低，但未观察到洗脱顺序的颠倒。还使用2-丁醇和2-戊醇对萘普生和氟比洛芬进行了研究。前者洗脱顺序颠倒，而后者没有。对于包括2-丙醇在内的高级醇改性剂，峰对称性较差，但可通过在醇改性剂中加入柠檬酸来改善。这些结果强调了在对映体选择性方法开发过程中以及优化色谱条件时研究对映体洗脱顺序的重要性。在-15至45℃范围内进行柱温的初步实验表明，在少数情况下，仅温度变化就会发生洗脱顺序的颠倒。
