Development of a column-switching high-performance liquid chromatography for kynurenine enantiomers and its application to a pharmacokinetic study in rat plasma |
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Authors: | Mitsuhashi Shogo Fukushima Takeshi Arai Kotaro Tomiya Masayuki Santa Tomofumi Imai Kazuhiro Toyo'oka Toshimasa |
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Institution: | a Division of Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan b Department of Bio-Analytical Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan c Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20, Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan |
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Abstract: | Kynurenine (KYN), a tryptophan metabolite, is a precursor of kynurenic acid, which is an antagonist of N-methyl-d-aspartate receptor. In this study, an enantiomeric separation of d,l-KYN derivatized with the benzofurazan fluorescence reagent 4-N,N-dimethylaminosulfonyl-7-fluoro-2,1,3-benzoxadiazole (DBD-F) (DBD-d,l-KYN) was first investigated by using a high-performance liquid chromatography (HPLC) with several chiral columns. As a consequence, DBD-d,l-KYN was enantiomerically separated on a cellulose-type chiral column (CHIRALCEL OJ-RH) with a mobile phase of H2O/CH3CN/MeOH (40/50/10) containing 0.1% acetic acid. Under this condition, the separation factor and resolution were 1.48 and 1.28, respectively. Next, a column-switching HPLC consisting of both octadecylsilica and chiral columns was developed and used to determine both d- and l-KYN enantiomers in 10 μL of rat plasma following the intraperitoneal administration of d,l-KYN to rats (10 mg kg−1). The result revealed that the concentration of l-KYN was higher than that of d-KYN, suggesting that d-KYN was eliminated faster than l-KYN. |
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Keywords: | d" target="_blank">d l-Kynurenine 4-N N-Dimethylaminosulfonyl-7-fluoro-2 1 3-benzoxadiazole CHIRALCEL OJ-RH Rat plasma Column-switching high-performance liquid chromatography |
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