Development of a high-throughput method for the determination of pharmacological levels of plasma d-serine

Jesse Alt, Camilo Rojas, Krystyna Wozniak, Ying Wu, Dana Ferraris, Takashi Tsukamoto, Barbara Slusher

Research output: Contribution to journalArticlepeer-review

Abstract

d-Serine administration has been shown to be effective for the treatment of schizophrenia symptoms. However, d-serine must be administered at high doses to observe clinical effects. This is due in large part to d-serine undergoing oxidation by d-amino acid oxidase (DAAO) before it reaches the brain. Consequently, coadministration of d-serine with a DAAO inhibitor has been suggested as a way to lower the dose of d-serine required to treat schizophrenia. During the characterization of DAAO inhibitors as potential drugs, inhibitors are evaluated in rodents for their ability to increase plasma d-serine levels after oral coadministration. Current high-performance liquid chromatography (HPLC)-based methodologies to measure d-serine in plasma are time-consuming and are not amenable to concomitant analysis of multiple samples. We report the characterization of a 96-well format assay to monitor d-serine in plasma that greatly expedites analysis time. The assay involves the use of strong cation exchange solid phase extraction (SPE) to isolate d-serine from plasma followed by quantitation of d-serine using the DAAO-catalyzed reaction. Plasma d-serine determination using this assay could also be used as pharmacodynamic marker and as biomarker.

Original languageEnglish (US)
Pages (from-to)106-109
Number of pages4
JournalAnalytical biochemistry
Volume419
Issue number2
DOIs
StatePublished - Dec 15 2011

Keywords

  • Schizophrenia
  • Solid phase extraction
  • d-Amino acid oxidase
  • d-Serine

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Development of a high-throughput method for the determination of pharmacological levels of plasma d-serine'. Together they form a unique fingerprint.

Cite this