Analytical enantioseparation of N-alkyl drugs by reversed-phase liquid chromatography with carboxymethyl-β-cyclodextrin as mobile phase additive.
Analytical enantioseparation of N-alkyl drugs by reversed-phase liquid chromatography with carboxymethyl-β-cyclodextrin as mobile phase additive.
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DOI：
10.1002/chir.23516
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发表时间：
2022-11
期刊：
影响因子：
2
通讯作者：
Haibo You;Benedict L. S. Chen;Liqun Fang;Tingting Lin;Ping Xu;Chu Chu-Chu;Shengqiang Tong
中科院分区：
文献类型：
--
作者：
Haibo You;Benedict L. S. Chen;Liqun Fang;Tingting Lin;Ping Xu;Chu Chu-Chu;Shengqiang Tong
合成并表征了5种取代度的羧甲基-β-环糊精（CM-β-CD）。以CM-β-CD为手性移动的添加剂，采用反相高效液相色谱法（RP-HPLC）实现了非尼拉敏、扑尔敏、拉贝洛尔、普萘洛尔、文拉法辛和反式帕罗西汀等6种含N-烷基的碱性药物对映体的拆分。优化了有机改性剂、pH值、不同取代度的CM-β-CD、CM-β-CD浓度等关键影响因素。移动的流动相为甲醇和含10 mmol L-1 CM-β-CD的10 mmol L-1磷酸盐缓冲液（pH 4.0）。随着CM-β-CD取代度的增加，6种外消旋药物的峰分离度逐渐增加。测定了CM-β-CD与对映体形成包合物的化学计量比和结合常数，结果表明，各包合物的化学计量比为1：1。
Carboxymethyl-β-cyclodextrins (CM-β-CDs) with five kinds of degrees of substitution were synthesized and characterized. Analytical enantioseparation of six basic drugs containing N-alkyl groups, including pheniramine, chlorpheniramine, labetalol, propranolol, venlafaxine, and trans-paroxol, was achieved by reversed-phase high-performance liquid chromatography (RP-HPLC) using the synthesized CM-β-CD as chiral mobile phase additives. Key influence factors were optimized, including organic modifier, pH value, CM-β-CD with different degrees of substitution, and concentration of CM-β-CD. The mobile phase was composed of methanol and 10 mmol L-1 of phosphate buffer pH 4.0 containing 10 mmol L-1 of CM-β-CD. Peak resolution for six racemic drugs was gradually increased with an increasing degree of substitution of the synthesized CM-β-CD. The stoichiometric ratio and binding constants for the inclusion complex formed by CM-β-CD and enantiomer were determined, which showed that the stoichiometric ratio for each inclusion complex was 1:1.