title: Development of a high-throughput method for the determination of pharmacological levels of plasma D-serine.
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.
authors: Brain Science Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors: Jesse
authors: J
authors: Alt
authors: Camilo
authors: C
authors: Rojas
authors: Krystyna
authors: K
authors: Wozniak
authors: Ying
authors: Y
authors: Wu
authors: Dana
authors: D
authors: Ferraris
authors: Takashi
authors: T
authors: Tsukamoto
authors: Barbara
authors: B
authors: Slusher
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002411:Cation Exchange Resins; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D057166:High-Throughput Screening Assays / Q000379:methods*; D051379:Mice; D012015:Reference Standards; D012694:Serine / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D052616:Solid Phase Extraction
chemical_list: D002411:Cation Exchange Resins; D004791:Enzyme Inhibitors; D012694:Serine; D003605:D-Amino-Acid Oxidase