Zhou Lili, Mao Bing, Ge Zhihong
Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, RY818-B-225, Rahway, NJ 07065, USA.
J Pharm Biomed Anal. 2008 Apr 14;46(5):898-906. doi: 10.1016/j.jpba.2007.07.008. Epub 2007 Jul 12.
The enantioselectivity of two protein chiral stationary phases, alpha1 acid glycoprotein (AGP) and ovomucoid protein (OVM) are compared. Neutral, basic and acidic pharmaceutical compounds were screened on both stationary phases. Selected parameters such as mobile phase pH, temperature, and organic modifier were varied in order to achieve chiral separations. Relations between the enantioselectivities of the two stationary phases and the properties of the compounds (acidity, basicity, structure of molecule) were also investigated. The OVM column tends to separate larger molecules better than the AGP column. Reversal of elution order for some compounds was observed on the two columns under similar experimental conditions, or with the same column as a function of pH and organic modifier. Many practical aspects were also discussed.
比较了两种蛋白质手性固定相，即α1酸性糖蛋白（AGP）和卵类粘蛋白（OVM）的对映体选择性。在这两种固定相上筛选了中性、碱性和酸性药物化合物。为了实现手性分离，改变了诸如流动相pH值、温度和有机改性剂等选定参数。还研究了两种固定相的对映体选择性与化合物性质（酸度、碱度、分子结构）之间的关系。OVM柱比AGP柱更倾向于更好地分离较大的分子。在相似的实验条件下，或在同一根柱子上，随着pH值和有机改性剂的变化，观察到一些化合物在两根柱子上的洗脱顺序发生了反转。还讨论了许多实际问题。
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