title: Evaluation of the metabolic chiral inversion of d-selenomethionine in rats by stable isotope dilution gas chromatography-mass spectrometry.
abstract: The stereoselective pharmacokinetics of selenomethionine enantiomers in rats has been studied to evaluate the chiral inversion of D-selenomethionine to the L-enantiomer. After bolus intravenous administration of D- or L-selenomethionine to rats, the plasma concentrations of these two enantiomers were determined by stereoselective gas chromatography-mass spectrometry with selected ion monitoring. This method involved derivatization of selenomethionine enantiomers with HCl in methanol to form methyl ester followed by N-acylation with (+)-α-methoxy-α-trifluoromethylphenylacetyl chloride to form the diastereomeric amide, and separation of the diastereomer on GC with an achiral column. Plasma concentrations of administered D- and L-selenomethionine declined with terminal half-lives of 96 ± 17 min and 91 ± 6 min, respectively. L-Selenomethionine appeared rapidly in plasma after administration of D-selenomethionine, whereas D-selenomethionine was not detected in plasma after administration of L-selenomethionine. The fraction of conversion of D-selenomethionine to L-selenomethionine was estimated to be 61.3 ± 14.5%. The present method evaluates the stereoselective pharmacokinetics of selenomethionine enantiomers, including the estimation of the metabolic chiral inversion.
authors.affiliation: Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: tmatsuka@juntendo.ac.jp.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Matsukawa
authors.affiliation: Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Goto
authors.affiliation: Center for the Advancement of Pharmaceutical Education, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachiouji, Tokyo 192-0392, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Shinohara
authors.affiliation: Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Research Institute for Cultural Science, Seisen University, 3-16-21 Higashi Gotanda, Shinagawa-ku, Tokyo 141-8642, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Shinohara
authors.affiliation: Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Omori
authors.affiliation: Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Ichida
authors.affiliation: Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D007553:Isotope Labeling / Q000379:methods*; D007668:Kidney / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012645:Selenomethionine / Q000097:blood* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D012645:Selenomethionine
keywords: Chiral inversion; GC–MS; Pharmacokinetics; Selenomethionine; Stable isotope