title: Simultaneous determination of serine enantiomers in plasma using Mosher's reagent and stable isotope dilution gas chromatography-mass spectrometry.
abstract: D-Serine is a co-agonist of the N-methyl-D-aspartate receptor in glutamate neurotransmission and has been proposed as a potential therapeutic agent for schizophrenia. However, D-serine also acts as a nephrotoxic substance in rats at high doses. To investigate the pharmacokinetics and toxicokinetics of D-serine, a method for the stereoselective determination of serine enantiomers in rat plasma was developed using GC-MS with selected ion monitoring (GC-MS-SIM). DL-[(2)H(3)]Serine was used as an internal standard to account for losses associated with the extraction, derivatization and chromatography. Serine enantiomers were purified by cation-exchange chromatography using BondElut SCX cartridge and derivatized with HCl in methanol to form methyl ester followed by subsequent N,O-diacylation with optically active (+)-α-methoxy-α-trifluoromethylphenylacetyl chloride to form epimeric amide. Quantitation was performed by SIM of the molecular-related ions of the epimers in the chemical ionization mode. The intra- and inter-day reproducibility of the assay was less than 5% for D-serine and 3% for L-serine. The method was successively applied to study the pharmacokinetics of D-serine in rats.
authors.affiliation: Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. hasegawa@ps.toyaku.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Nami
authors.initials: N
authors.lastname: Masuda
authors.forename: Takao
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Ichida
mesh_terms: D000818:Animals; D002852:Chromatography, Ion Exchange; D003903:Deuterium / Q000032:analysis / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D007553:Isotope Labeling; D008297:Male; D010648:Phenylacetates / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012694:Serine / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D013237:Stereoisomerism
chemical_list: D010648:Phenylacetates; D012694:Serine; C108322:Mosher's acid; D003903:Deuterium