Gamma-aminobutyric acid (GABA) and its precursor glutamic acid are important neurotransmitters. Both are also present in peripheral tissues and the circulation, where abnormal plasma concentrations have been linked to specific mental disorders. In addition to endogenous synthesis, GABA and glutamic acid can be obtained from dietary sources. An increasing number of studies suggest beneficial cardio-metabolic effects of GABA intake, and therefore GABA is being marketed as a food supplement. The need for further research into their health effects merits accurate and sensitive methods to analyze GABA and glutamic acid in plasma. To this end, an ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of GABA and glutamic acid in human plasma. Samples were prepared by a protein precipitation step and subsequent solid phase extraction using acetonitrile. Chromatographic separation was achieved on an Acquity UPLC HSS reversed phase C18 column using gradient elution. Analytes were detected using electrospray ionization and selective reaction monitoring. Standard curve concentrations for GABA ranged from 3.4 to 2500 ng/mL and for glutamic acid from 30.9 ng/mL to 22,500 ng/mL. Within- and between-day accuracy and precision were <10% in quality control samples at low, medium and high concentrations for both GABA and glutamic acid. GABA and glutamic acid were found to be stable in plasma after freeze–thaw cycles and up to 12 months of storage. The validated method was applied to human plasma from 17 volunteers. The observed concentrations ranged between 11.5 and 20.0 ng/ml and 2269 and 7625 ng/ml for respectively GABA and glutamic acid. The reported method is well suited for the measurement of plasma GABA and glutamic acid in pre-clinical or clinical studies.

γ-氨基丁酸（GABA）及其前体谷氨酸是重要的神经递质。两者也都存在于外周组织和循环系统中，其中血浆异常浓度与特定的精神障碍有关。除内源性合成外，还可从饮食中获得GABA和谷氨酸。越来越多的研究表明摄入GABA具有有益的心脏代谢作用，因此GABA被作为食品补充剂上市。需要对它们的健康影响进行进一步研究，从而需要准确，灵敏的方法来分析血浆中的GABA和谷氨酸。为此，开发了一种采用串联质谱联用的超高压液相色谱（UPLC-MS / MS）方法，并验证了该方法可用于定量测定人血浆中的GABA和谷氨酸。通过蛋白质沉淀步骤并随后使用乙腈进行固相萃取来制备样品。使用梯度洗脱在Acquity UPLC HSS反相C18色谱柱上进行色谱分离。使用电喷雾电离和选择性反应监测检测分析物。GABA的标准曲线浓度范围为3.4至2500 ng / mL，谷氨酸的标准曲线浓度范围为30.9 ng / mL至22,500 ng / mL。对于GABA和谷氨酸，在低，中和高浓度的质量控制样品中，日间和日间准确性和精密度均<10％。发现冻融循环后的GABA和谷氨酸在血浆中稳定，并可以保存12个月。经验证的方法应用于17名志愿者的人体血浆。观察到的浓度范围为11.5至20。GABA和谷氨酸分别为0 ng / ml和2269和7625 ng / ml。报告的方法非常适合在临床前或临床研究中测量血浆GABA和谷氨酸。