DEVELOPMENT OF A NEW CHIRAL SEPARATION COLUMN AND ITS APPLICATION
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- MANO Nariyasu
- Analytical Research Laboratories, Eisai Co., Ltd
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- ODA Yoshiya
- Analytical Research Laboratories, Eisai Co., Ltd
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- ASAKAWA Naoki
- Analytical Research Laboratories, Eisai Co., Ltd
Bibliographic Information
- Other Title
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- 新規光学分割カラムの開発と薬物動態研究への応用
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Abstract
A new chiral separation column using flavoprotein from chicken egg white was developed for HPLC. This column allow to use under the aqueous condition and can separate drug enantiomers with a broad range. And this column has both a moderate non-specific retention and a enantioselectivity, so it can separate not only enantiomers but also analogues such as metabolites. Interactions between drug enantiomers (ketoprofen as a model) and chiral discrimination region on flavoprotein was investigated using affinity capillary electrophoresis combined with circular dichroism and chemical modification of flavoprotein. The chiral discrimination region was concluded to consist of α-helix structure, and required π-π interaction of a tryptophan residue with the aromatic ring of ketoprofen and ionic interaction of the carboxyl group of ketoprofen with an amino group of the protein for chiral separation.<BR> In order to demonstrate an application of flavoprotein column for pharmacokinetic study, a column-switching HPLC method with direct injection of a large volume of plasma was developed for simultaneous determination of E3810 and its metabolites. This method is simple, rapid, accurate, and precise, and should be very useful for enantioselective pharmacokinetic studies.
Journal
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 13 (supplement), 128-129, 1998
The Japanese Society for the Study of Xenobiotics
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Details 詳細情報について
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- CRID
- 1390001204669927168
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- NII Article ID
- 10007629708
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- NII Book ID
- AN10144117
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- ISSN
- 09161139
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed