Development of a column-switching high-performance liquid chromatography for kynurenine enantiomers and its application to a pharmacokinetic study in rat plasma.

作者: Shogo Mitsuhashi , Takeshi Fukushima , Kotaro Arai , Masayuki Tomiya , Tomofumi Santa

DOI: 10.1016/J.ACA.2007.01.033

关键词: KynurenineHigh-performance liquid chromatographyTryptophanChemistryChromatographyMetaboliteAcetic acidKynurenic acidFluorescence spectrometryEnantiomer

摘要: Abstract Kynurenine (KYN), a tryptophan metabolite, is precursor of kynurenic acid, which an antagonist N -methyl- d -aspartate receptor. In this study, enantiomeric separation d,l -KYN derivatized with the benzofurazan fluorescence reagent 4- N,N -dimethylaminosulfonyl-7-fluoro-2,1,3-benzoxadiazole (DBD-F) (DBD- -KYN) was first investigated by using high-performance liquid chromatography (HPLC) several chiral columns. As consequence, DBD- enantiomerically separated on cellulose-type column (CHIRALCEL OJ-RH) mobile phase H 2 O/CH 3 CN/MeOH (40/50/10) containing 0.1% acetic acid. Under condition, factor and resolution were 1.48 1.28, respectively. Next, column-switching HPLC consisting both octadecylsilica columns developed used to determine - l enantiomers in 10 μL rat plasma following intraperitoneal administration , rats (10 mg kg −1 ). The result revealed that concentration higher than -KYN, suggesting eliminated faster -KYN.

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