吲哚洛尔与环糊精相互作用的高效液相色谱及溶解度研究

HPLC and solubility study of the interaction between pindolol and cyclodextrins.

作者信息

Gazpio Carmen, Sánchez Miguel, García-Zubiri Iñigo X, Vélaz Itziar, Martínez-Ohárriz Cristina, Martín Carmen, Zornoza Arantza

机构信息

Departamento de Química y Edafología, Facultad de Ciencias, Universidad de Navarra, Irunlarrea s/n, Pamplona 31080, Spain.

出版信息

J Pharm Biomed Anal. 2005 Mar 9;37(3):487-92. doi: 10.1016/j.jpba.2004.11.008. Epub 2004 Dec 10.

DOI:10.1016/j.jpba.2004.11.008

PMID:15740908

Abstract

The complexation with beta-cyclodextrin (beta-CD) has been investigated using reversed-phase liquid chromatography. The compounds tested have been pindolol and, for comparison purposes, indole and 4-methoxyindole. The retention behaviour has been analysed on a Kromasil 100 C18 column and the mobile phase used was methanol-pH 6 phosphate buffer (15/85v/v) in which beta-CD was incorporated as a mobile phase additive. The decrease in the retention times with increasing concentrations of beta-CD enables the determination of the apparent stability constants of the complexes. In addition, the low solubility of pindolol, a weak base, in pH 12 aqueous solution has been improved by complexation with different cyclodextrins. The solubility enhancements with 1.4 x 10(-2) M beta-, hydroxypropyl-beta, and gamma-CD have been 1.9, 1.8 and 1.4-fold, respectively, with 2.4 x 10(-2) M methyl-beta-CD it was 2.8-fold whilst no effect was observed with alpha-CD. The stability constants of the complexes at pH 12 have been determined from the solubility isotherms.

摘要

已使用反相液相色谱法研究了与β-环糊精（β-CD）的络合作用。所测试的化合物有吲哚洛尔，为作比较还包括吲哚和4-甲氧基吲哚。在Kromasil 100 C18柱上分析了保留行为，所用流动相为甲醇 - pH 6磷酸盐缓冲液（15/85 v/v），其中加入了β-CD作为流动相添加剂。随着β-CD浓度增加保留时间缩短，据此可测定络合物的表观稳定常数。此外，弱碱吲哚洛尔在pH 12水溶液中的低溶解度通过与不同环糊精络合得到了改善。1.4×10⁻² M的β-、羟丙基-β-和γ-环糊精使溶解度分别提高了1.9倍、1.8倍和1.4倍，2.4×10⁻² M的甲基-β-环糊精使其提高了2.8倍，而α-环糊精未观察到效果。已根据溶解度等温线测定了pH 12时络合物的稳定常数。