Add time:08/19/2019         Source:sciencedirect.com

An on-line frontal analysis HPLC system was developed for the determination of the unbound concentrations of SEMOTIADIL (cas 116476-13-2), 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 α1-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.

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