Rodriguez Rosas M E, Shibukawa A, Ueda K, Nakagawa T
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
J Pharm Biomed Anal. 1997 Jun;15(9-10):1595-601. doi: 10.1016/s0731-7085(96)02053-5.
An on-line frontal analysis HPLC system was developed for the determination of the unbound concentrations of semotiadil, a new calcium antagonist with non-dihydropyridine structure, and its antipode (Levosemotiadil), and was applied to the enantioselective investigation of their plasma protein binding properties. This system consists of a high-performance frontal analysis (HPFA) column, an extraction column, and an analytical column, which are connected via two switching valves. After the direct injection of the sample solution into the HPFA column, the drug was eluted as a zonal peak with a plateau region. The unbound drug concentration was determined as the drug concentration in the plateau. As low as 1.04 nM of the unbound drug was determined with good reproducibility. Semotiadil (R-isomer) and levosemotiadil (S-isomer) are bound strongly and enantioselectively to human serum albumin (HSA) and human alpha 1-acid glycoprotein (AGP), and the enantioselectivity was reversed between these plasma proteins. While HSA binds S-isomer more strongly than the antipode, human AGP binds R-isomer more strongly. In human plasma, the unbound drug fraction was less than 1%, and the enantioselectivity was similar to that observed in AGP solution.
开发了一种在线前沿分析高效液相色谱系统，用于测定新型非二氢吡啶结构钙拮抗剂塞莫替地尔及其对映体（左旋塞莫替地尔）的游离浓度，并将其应用于对它们血浆蛋白结合特性的对映选择性研究。该系统由一根高效前沿分析（HPFA）柱、一根萃取柱和一根分析柱组成，它们通过两个切换阀连接。将样品溶液直接注入HPFA柱后，药物以带有平台区的带状峰形式洗脱。游离药物浓度被确定为平台区的药物浓度。可测定低至1.04 nM的游离药物，且重现性良好。塞莫替地尔（R-异构体）和左旋塞莫替地尔（S-异构体）与人类血清白蛋白（HSA）和人类α1-酸性糖蛋白（AGP）有强烈且对映选择性的结合，并且在这些血浆蛋白之间对映选择性相反。虽然HSA对S-异构体的结合比对映体更强，但人类AGP对R-异构体的结合更强。在人血浆中，游离药物分数小于1%，且对映选择性与在AGP溶液中观察到的相似。
