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.

Application of TLC, HPLC and GC methods to the study of amino acid and peptide enantiomers: a review

“…GC‐MS analysis was performed using quadrupole with selected ion monitoring (GC‐MS‐SIM) on an SPB‐1 column (15 m × 0.25 mm). Helium was used as a carrier gas (Hasegawa et al ., ).…”

“…The naturally found protein amino acids are generally composed of l ‐enantiomers. d ‐Enantiomers can be found in plants, bacterial cells or in several antibiotics (Hasegawa et al ., ). The amino acid enantiomers have identical chemical and physical properties but possess different biological activities.…”

Liquid and supercritical fluid chromatographic enantioseparation of Nα‐Fmoc proteinogenic amino acids on Cinchona alkaloid-based chiral stationary phases

“…The natural protein amino acids are generally L-enantiomers. D-Enantiomers can be found in plants, bacterial cells or in several antibiotics [72]. All of them, except glycine, contain at least one stereogenic center.…”