Development of a high-throughput method for the determination of pharmacological levels of plasma D-serine.
Development of a high-throughput method for the determination of pharmacological levels of plasma D-serine.
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DOI：
10.1016/j.ab.2011.08.018
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发表时间：
2011-12-15
影响因子：
2.9
通讯作者：
Slusher B
中科院分区：
文献类型：
--
作者：
Alt J;Rojas C;Wozniak K;Wu Y;Ferraris D;Tsukamoto T;Slusher B
d -丝氨酸已被证明对治疗精神分裂症症状有效。然而，为了观察临床效果，d -丝氨酸必须以高剂量施用。这在很大程度上是由于d -丝氨酸在到达大脑之前被d -氨基酸氧化酶（DAAO）氧化。因此，建议将d -丝氨酸与DAAO抑制剂共同施用，作为降低治疗精神分裂症所需d -丝氨酸剂量的一种方法。在表征DAAO抑制剂作为潜在药物的过程中，在啮齿动物中评估了抑制剂在口服联合给药后增加血浆d -丝氨酸水平的能力。目前基于高效液相色谱法测量血浆中d -丝氨酸的方法耗时长，不适合同时分析多个样品。我们报告了一种96孔格式检测血浆中d -丝氨酸的特性，大大加快了分析时间。该分析包括使用强阳离子交换固相萃取（SPE）从血浆中分离d -丝氨酸，然后使用DAAO催化反应定量d -丝氨酸。血浆d -丝氨酸的测定也可作为药效学指标和生物标志物。
D-serine administration has been shown to be effective for the treatment of schizophrenia symptoms. However, D-serine has to be administered at high doses in order to observe clinical effects. This is in large part due to D-serine undergoing oxidation by D-amino acid oxidase (DAAO) before it reaches the brain. Consequently, co-administration 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 co-administration. Current 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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影响因子：
--
作者：
Brandish, Philip E.;Chiu, Chi-Sung;Zheng, Wei
通讯作者：
Zheng, Wei
影响因子：
1.8
作者：
Fukushima, T;Kawai, J;Toyo'oka, T
通讯作者：
Toyo'oka, T
影响因子：
10.6
作者：
Tsai, GC;Yang, PC;Coyle, JT
通讯作者：
Coyle, JT
DOI：
10.1124/jpet.108.147884
发表时间：
2009-03-01
影响因子：
3.5
作者：
Smith, Sean M.;Uslaner, Jason M.;Hutson, Peter H.
通讯作者：
Hutson, Peter H.
影响因子：
10.6
作者：
Heresco-Levy, U;Javitt, DC;Ermilov, M
通讯作者：
Ermilov, M