Tang Y
Division of Drug Analysis, U.S. Food and Drug Administration, St. Louis, Missouri 63101, USA.
Chirality. 1996;8(1):136-42. doi: 10.1002/(SICI)1520-636X(1996)8:1<136::AID-CHIR20>3.0.CO;2-N.
Eight randomly selected pharmaceuticals, which included ibuprofen, ketoprofen, albuterol, acebutolol, propafenone, betaxolol, methylphenidate, and homatropine, were directly separated on a cellulose tris(4-methylbenzoate) chiral stationary phase (CSP) without derivatization via normal phase mode HPLC. Enantioresolution was achieved by the optimization of the type and the ratio of mobile phase modifiers and additives. The modifiers included alcohols; the mobile phase additives were trifluoroacetic acid (TFA) and triethylamine (TEA). It was found that methanol and ethanol were superior to isopropanol as mobile phase modifiers for enhancing chiral separation of some of the chiral drugs. The results also demonstrated that TFA has a dominant effect on chiral separations for both acidic and basic chiral drugs, although for some basic drug such as homatropine, TEA was more beneficial at improving enantioseparation. The separation of acebutolol enantiomers was achieved for the first time by adding both TFA and TEA to the mobile phase. The purpose of this paper is to demonstrate that the applicability of cellulose based CSPs can be expanded by controlling the mobile phase compositions through the addition of trace amounts of achiral additives and the selection of the appropriate alcoholic modifier.
随机选取了8种药物，包括布洛芬、酮洛芬、沙丁胺醇、醋丁洛尔、普罗帕酮、倍他洛尔、哌醋甲酯和后马托品，在纤维素三（4 - 甲基苯甲酸酯）手性固定相（CSP）上直接分离，无需衍生化，采用正相模式高效液相色谱法。通过优化流动相改性剂和添加剂的类型及比例实现对映体拆分。改性剂包括醇类；流动相添加剂为三氟乙酸（TFA）和三乙胺（TEA）。结果发现，作为流动相改性剂，甲醇和乙醇在增强某些手性药物的手性分离方面优于异丙醇。结果还表明，TFA对酸性和碱性手性药物的手性分离均有主导作用，不过对于某些碱性药物如后马托品，TEA在改善对映体分离方面更有益。通过在流动相中同时加入TFA和TEA，首次实现了醋丁洛尔对映体的分离。本文的目的是证明通过添加痕量非手性添加剂和选择合适的醇类改性剂来控制流动相组成，可以扩大基于纤维素的CSP的适用性。
