RT Journal Article SR Electronic T1 Assessment of the Metabolic Chiral Inversion ofd-Leucine in Rat by Gas Chromatography-Mass Spectrometry Combined with a Stable Isotope Dilution Analysis JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 920 OP 924 VO 28 IS 8 A1 Hiroshi Hasegawa A1 Takehisa Matsukawa A1 Yoshihiko Shinohara A1 Takao Hashimoto YR 2000 UL http://dmd.aspetjournals.org/content/28/8/920.abstract AB The stereoselective pharmacokinetics of leucine enantiomers in rats has been investigated to evaluate the inversion ofd-leucine to l-enantiomer. After a bolus i.v. administration of d- orl-[2H7]leucine to rats, blood samples were obtained over 6 h after administration and analyzed by a stereoselective gas chromatography-mass spectrometry method. Racemic [2H3]leucine was used as an internal standard. The method involved methyl esterification and subsequent chiral derivatization with (+)-α-methoxy-α-trifluoromethylphenylacetyl chloride to form the diastereomeric amide. The derivatization made possible the separation of leucine enantiomers with good gas chromatographic behavior. Plasma concentration of both d- andl-[2H7]leucine declined biexponentially, with elimination half-lives of 60 and 14 min, respectively. In contrast to the l-enantiomer, thed-enantiomer had a lower systemic clearance. Whend-[2H7]leucine was administered, the l-enantiomer was found to rapidly appear in plasma. About 30% of an administered dose of the d-isomer was stereospecifically inverted to the l-enantiomer. There was no measurable inversion of the l- tod-enantiomer. This methodology has made it possible to evaluate the pharmacokinetics of each enantiomer of amino acids and estimate of chiral inversion after administration ofd-amino acids. The American Society for Pharmacology and Experimental Therapeutics