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- Serine 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.
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Authors | Jesse Alt, Camilo Rojas, Krystyna Wozniak, Ying Wu, Dana Ferraris, Takashi Tsukamoto, Barbara Slusher |
Journal | Analytical biochemistry
(Anal Biochem)
Vol. 419
Issue 2
Pg. 106-9
(Dec 15 2011)
ISSN: 1096-0309 [Electronic] United States |
PMID | 21889486
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2011 Elsevier Inc. All rights reserved. |
Chemical References |
- Cation Exchange Resins
- Enzyme Inhibitors
- Serine
- D-Amino-Acid Oxidase
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Topics |
- Administration, Oral
- Animals
- Cation Exchange Resins
- D-Amino-Acid Oxidase
(antagonists & inhibitors, metabolism)
- Enzyme Assays
- Enzyme Inhibitors
(administration & dosage, pharmacology)
- High-Throughput Screening Assays
(methods)
- Mice
- Reference Standards
- Serine
(blood, chemistry, isolation & purification)
- Solid Phase Extraction
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