Publication: Plasma protein binding study of oxybutynin by high-performance frontal analysis
Issued Date
2002
Resource Type
Language
eng
File Type
application/pdf
No. of Pages/File Size
221404 bytes
ISSN
1570-0232
Rights
Mahidol University
Bibliographic Citation
Journal of Chromatography B. Vol.768, No.1 (2002), 177-188.
Suggested Citation
Akimasa Shibukawa, Nobuko Ishizawa, Tomako Kimura, Yuki Sakamoto, Kanae Ogita, Yuka Matsuo, Yukihiro Kuroda, Chutima Matayatsuk, Terumichi Nakagawa, Irving W. Wainer Plasma protein binding study of oxybutynin by high-performance frontal analysis. Journal of Chromatography B. Vol.768, No.1 (2002), 177-188.. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/62279
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Title
Plasma protein binding study of oxybutynin by high-performance frontal analysis
Abstract
Plasma protein binding of oxybutynin (OXY) was investigated quantitatively and enantioselectively using highperformance
frontal analysis (HPFA). An on-line HPLC system which consists of HPFA column, extraction column and
analytical column was developed to determine the unbound concentrations of OXY enantiomers in human plasma, in human
serum albumin (HSA) solutions, and in human a -acid glycoprotein (AGP) solutions. OXY is bound in human plasma 1
strongly and enantioselectively. The bound drug fraction in human plasma containing 2–10 mM (R)- or (S)-OXY was higher
than 99%, and the unbound fraction of (R)-OXY was 1.56 times higher than that of (S)-isomer. AGP plays the dominant role
in this strong and enantioselective plasma protein binding. The total binding affinities (nK) of (R)- and (S)-OXY to AGP
6 7 21 4 were 6.86310 and 1.53310 M , respectively, while the nK values of (R)- and (S)-OXY to HSA were 2.64310 and
4 21 2.19310 M , respectively. The binding affinity of OXY to AGP is much higher than that to HSA, and shows high
enantioselectivity (S/R ratio of nK values is 2.2). It was found that both enantiomers are bound competitively at the same
binding site on an AGP molecule. The binding property between OXY and low density lipoprotein (LDL) was investigated
by using the frontal analysis method incorporated in high-performance capillary electrophoresis (HPCE/FA). It was found
the binding is non-saturable and non-enantioselective.