Enantioseparation of five racemic N-alkyl drugs by reverse phase HPLC using sulfobutylether-β-cyclodextrin as a chiral mobile phase additive
Enantioseparation of five racemic N-alkyl drugs by reverse phase HPLC using sulfobutylether-β-cyclodextrin as a chiral mobile phase additive
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DOI：
10.1002/jssc.202200004
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发表时间：
2022-04-04
影响因子：
3.1
通讯作者：
Tong, Shengqiang
中科院分区：
文献类型：
--
作者：
Chen, Ben;You, Haibo;Tong, Shengqiang
采用反相高效液相色谱法，以磺基丁醚-β-环糊精为手性移动的添加剂，研究了五种N-烷基药物盐酸莫西汀、拉贝洛尔、盐酸文拉法辛、反式帕罗索和硫酸阿托品的对映体分离。考察了移动的相组成、环糊精浓度、柱温等因素对保留值和对映选择性的影响。采用紫外分光光度法测定了甲醇、乙腈和磺丁基醚-β-环糊精在25 ℃下的表观形成常数分别为2.90 x 10（-3）和1.00 x 10（-4）L mmol（-1）。采用Van 't霍夫作图法研究了包合物形成过程中对映体与固定相相互作用的热力学参数。分别采用两种保留模型对五种外消旋体与磺丁基醚-β-环糊精的包合作用进行了评价。第二个模型与盐酸氟西汀、拉贝洛尔和文拉法辛的保留行为雅阁，而第一个模型与反式帕罗西汀和硫酸阿托品的保留行为更吻合。在选定的移动的相中，包合物的化学计量比为1：1。
Analytical enantioseparations of five N-alkyl drugs, fluoxetine hydrochloride, labetalol, venlafaxine hydrochloride, trans-paroxol, and atropine sulfate, were investigated by reverse phase high-performance liquid chromatography with sulfobutylether-beta-cyclodextrin as chiral mobile phase additive. Effects of various factors such as composition of mobile phase, concentration of cyclodextrins, and column temperature on retention and enantioselectivity were studied. Apparent formation constant between methanol, acetonitrile, and sulfobutylether-beta-cyclodextrin were determined to be 2.90 x 10(-3) and 1.00 x 10(-4) L mmol(-1) under 25 degrees C using UV-spectrophotometry. Van't Hoff plots were used to investigate thermodynamic parameters for enantiomers-stationary phase interaction and formation of inclusion complex. Two retention models were employed individually for evaluation of inclusion complexation between five racemates and sulfobutylether-beta-cyclodextrin. The second model with complex adsorption was more accord with the retention behavior of fluoxetine hydrochloride, labetalol, and venlafaxine hydrochloride enantiomers, while the first model was more consistent with the retention behaviors of trans-paroxol and atropine sulfate. In the selected mobile phase, stoichiometric ratio for both of inclusion complex was found to be 1:1.