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一种用于在高效液相色谱中检测β-肾上腺素能药物和β-肾上腺素能阻滞剂的新型电位分析法。

A novel potentiometric approach for detection of beta-adrenergics and beta-adrenolytics in high-performance liquid chromatography.

作者信息

Bazylak Grzegorz, Nagels Luc J

机构信息

Department of Drug Chemistry, Faculty of Pharmacy, Ludwik Rydygier Medical University, Jagiellonska 13, PL-85-067 Bydgoszcz, Poland.

出版信息

Farmaco. 2003 Aug;58(8):591-603. doi: 10.1016/S0014-827X(03)00096-X.

Abstract

Potentiometric approach enabling sensitive and reliable detection for a series of 20 autonomic beta-adrenergic ligands with the use of poly(vinyl chloride) (PVC) based liquid membrane electrode coatings in the normal-bore cation exchange HPLC and narrow-bore reversed phase HPLC system is presented. It was found that in both kinds of HPLC modes with a contemporary hybrid polymer-silica packings an application of electrodes containing a tetrakis(p-chlorophenyl)borate (TCPB) gives limits of detection below to 8.0x10(-7) mol l(-1) (injected concentrations). In case of highly hydrophobic beta-adrenergic drugs the use of binary aqueous mobile phases with high concentrations of acetonitrile (up to 25% v/v) shifting an observable detection limits (DL) down to 2.0x10(-8) mol l(-1), especially for electrodes with addition of trioctylated alpha-cyclodextrin. The characteristics of developed potentiometric detectors was established by proposed a quantitative structure-potentiometric response relationships (QSPRRs) for a series of diversified beta-adrenergic compounds and for a set of the PVC based electrodes using TCPB alone as well as in combination with trioctylated alpha-cyclodextrin, dibenzo-18-crown-6, or calix[6]arene hexaethylester as the neutral macrocycle ionophore. A highly significant QSPRRs equations were obtained leading to reasonable prediction of the DL of specified electrodes in terms of the computationally derived set of molecular descriptors of beta-adrenergics and beta-blocking agents and similar amino alcohol type xenobiotics.

摘要

本文介绍了一种电位分析法,该方法利用基于聚氯乙烯(PVC)的液膜电极涂层,在常规内径阳离子交换高效液相色谱(HPLC)和窄内径反相HPLC系统中,能够对一系列20种自主神经β-肾上腺素能配体进行灵敏且可靠的检测。研究发现,在两种采用当代混合聚合物-硅胶填料的HPLC模式中,应用含有四(对氯苯基)硼酸盐(TCPB)的电极时,检测限低至8.0×10⁻⁷ mol·L⁻¹(进样浓度)。对于高度疏水的β-肾上腺素能药物,使用高浓度乙腈(高达25% v/v)的二元水相流动相可将可观测检测限(DL)降至2.0×10⁻⁸ mol·L⁻¹,特别是对于添加了三辛基化α-环糊精的电极。通过提出一系列多样化的β-肾上腺素能化合物以及一组仅使用TCPB以及与三辛基化α-环糊精、二苯并-18-冠-6或杯[6]芳烃六乙酯作为中性大环离子载体的PVC基电极的定量结构-电位响应关系(QSPRRs),确定了所开发电位检测器的特性。获得了高度显著的QSPRRs方程,从而能够根据β-肾上腺素能药物、β-阻滞剂和类似氨基醇类外源性物质的计算得出的分子描述符集,合理预测特定电极的检测限。

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