title: Bioanalytical method for the simultaneous determination of D- and L-serine in human plasma by LC/MS/MS.
abstract: D-Serine is an endogenous modulator of N-methyl-D-aspartate (NMDA) receptors. Plasma concentrations of D-serine and the ratio of D-serine to total serine may be used as clinically-translatable biomarkers in NMDA receptor-related disease. We developed a highly sensitive and specific method using high performance liquid chromatography tandem mass spectrometry (LC/MS/MS) for the simultaneous determination of the D- and L-isomers of serine in human plasma. Since D- and L-serine are endogenous components, phosphate buffered saline was used as the surrogate matrix. D- and L-serine in human plasma and PBS were treated by cationic exchange solid phase extraction. D-Serine (m/z 106.1 > 60.0), L-serine (m/z 106.1 > 60.1) and DL-serine-d3 (m/z 109.1 > 63.0) were detected using a multiple reaction monitoring. The enantiomer separation of D- and L-serine was successfully achieved without any derivatization step using tandemly-arranged and ice-cold CROWNPAK CR-I(+) columns with an isocratic mobile phase comprised of 0.3% trifluoroacetic acid in 10% acetonitrile. The standard curves were linear throughout the calibration range with 0.01-10 μg/mL (D-serine) and 0.1-100 μg/mL (L-serine), respectively. Intra-day and inter-day precision and accuracy of the quality control samples were within relative standard deviations of less than 15%. The endogenous concentrations of D- and L-serine in human plasma were 0.124-0.199 and 7.97-13.1 μg/mL, respectively.
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical, Fujisawa, Kanagawa, 251-8555, Japan. Electronic address: hiroshi.sugimoto1@takeda.com.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugimoto
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical, Fujisawa, Kanagawa, 251-8555, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kakehi
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical, Fujisawa, Kanagawa, 251-8555, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Jinno
mesh_terms: D002851:Chromatography, High Pressure Liquid; D006801:Humans; D012694:Serine / Q000097:blood*; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D012694:Serine
keywords: Bioanalytical method; Biomarker; Enantiomer separation; LC/MS/MS; Surrogate matrix; d- and l-serine