Direct Quantitation of D-serine in Human Plasma by Enantioselective Liquid Chromatography with Tandem Mass Spectrometry and its Application to a Clinical Study

D-serine, (2R)-2-amino-3-hydroxy-propanoic acid, as shown in Figure 1a, is a well-known endogenous co-agonist of the N-methyl-D-aspartate-type glutamate receptor (NMDA receptor) that belongs to a family of neurotransmitter receptors in nerve cells and plays key roles in learning, memory and neuroplasticity functions. D-serine is a neuromodulator that regulates the activities of neurons. Because of the importance of NMDA receptor in brain activities, D-serine levels in human plasma, cerebrospinal fluid (CSF), and urine are often considered as a biomarker in drug development for neuropathic pain, cognitive deficits by acute stress or impairment associated with schizophrenia (CIAS), and Alzheimer’s disease (AD) etc.

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