HIGH-PERFORMANCE FRONTAL ANALYSIS FOR THE STUDY OF PROTEIN-BINDING OF TROGLITAZONE (CS-045) IN ALBUMIN SOLUTION AND IN HUMAN PLASMA

被引:52
作者
SHIBUKAWA, A [1 ]
SAWADA, T [1 ]
NAKAO, C [1 ]
IZUMI, T [1 ]
NAKAGAWA, T [1 ]
机构
[1] SANKYO CO LTD,PROD DEV LABS,SHINAGAWA KU,TOKYO 140,JAPAN
关键词
D O I
10.1016/0021-9673(94)00929-4
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
An on-line frontal analysis HPLC system was developed for the determination of the unbound concentration of troglitazone (CS-045), a new oral antidiabetic agent, in human serum albumin (HSA) solution and in human plasma. 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 0.3 nM unbound CS-045 was determined with good reproducibility. It was found that CS-045 strongly binds with HSA, and the bound fraction in the 550 mu M HSA solution was 99.93%, which was very close to that in human plasma (99.89%). The bound fractions were constant within the total drug concentration range of 1-10 mu M in the HSA solution and 250 nM-10 mu M in human plasma.
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页码:337 / 343
页数:7
相关论文
共 13 条
[1]  
Fujiwara, Yoshioka, Yoshioka, Ushiyama, Horikoshi, Diabetes, 37, pp. 1549-1558, (1988)
[2]  
Meyer, Guttman, J. Pharm. Sci., 57, pp. 895-918, (1968)
[3]  
Vallner, J. Pharm. Sci., 66, pp. 447-465, (1977)
[4]  
Kwong, Clin. Chim. Acta, 151, pp. 193-216, (1985)
[5]  
Shibukawa, Nakagawa, Nishimura, Miyake, Tanaka, Chem. Pharm. Bull., 37, pp. 702-706, (1989)
[6]  
Shibukawa, Nishimura, Nomura, Kuroda, Nakagawa, Chem. Pharm. Bull., 38, pp. 443-447, (1990)
[7]  
Shibukawa, Nagao, Kuroda, Nakagawa, Anal. Chem., 62, pp. 712-716, (1990)
[8]  
Nishimura, Shibukawa, Nakagawa, High-performance frontal analysis for the determination of the free drug concentration in protein binding equilibrium using porous polymer stationary phase., Analytical Sciences, 6, pp. 355-359, (1990)
[9]  
Shibukawa, Terakita, He, Nakagawa, J. Pharm. Sci., 81, pp. 710-715, (1992)
[10]  
Terakita, Shibukawa, Nakagawa, Micro High-Performance Frontal Analysis for Simultaneous Determination of Unbound and Total Carbamazepine Concentrations in Protein Binding Equilibrium., Analytical Sciences, 9, pp. 229-232, (1993)