Olsen B A, Wirth D D, Larew J S
Lily Research Laboratories, Eli Lilly and Company, Lafayette, IN 47902, USA.
J Pharm Biomed Anal. 1998 Aug;17(4-5):623-30. doi: 10.1016/s0731-7085(98)00050-8.
Chromatographic methods using chiral stationary phases have been developed for the separation of fluoxetine hydrochloride enantiomers. Ovomucoid and tris(3,5-dimethylphenyl carbamate) cellulose stationary phases were used in the reversed- and normal-phase modes, respectively. Acceptable isomer separation was achieved at pH 3.5 with the ovomucoid phase. Isopropyl alcohol and methyl-tert- butyl ether mobile phase modifiers each provide complete resolution using the derivatized cellulose column. Better separation robustness was obtained with a column temperature of 1 degree C the isopropyl alcohol modifier. The methyl-tert-butyl ether system was robust at room temperature. Differences in relative enantiomer amounts of as little as 2% could be determined. The chromatographic conditions provided a much more discriminating test compared to an optical rotation method proposed for pharmacopeial use which had difficulty distinguishing individual enantiomers. The chiral chromatographic conditions were also applied to capsule formulations to demonstrate the presence of racemic fluoxetine hydrochloride.
已开发出使用手性固定相的色谱方法来分离盐酸氟西汀对映体。分别在反相和正相模式下使用卵类粘蛋白和三（3,5-二甲基苯基氨基甲酸酯）纤维素固定相。使用卵类粘蛋白相在pH 3.5时实现了可接受的异构体分离。异丙醇和甲基叔丁基醚流动相改性剂各自使用衍生化纤维素柱提供了完全分离。使用异丙醇改性剂，在柱温为1℃时获得了更好的分离稳健性。甲基叔丁基醚系统在室温下很稳健。可以测定低至2%的对映体相对量差异。与药典中提出的用于区分单个对映体存在困难的旋光法相比，该色谱条件提供了更具区分性的测试。手性色谱条件也应用于胶囊制剂，以证明存在外消旋盐酸氟西汀。
