On This Day … 03 June

People (Births)

  • 1873 – Otto Loewi, German-American pharmacologist and psychobiologist, Nobel Prize laureate (d. 1961).

Otto Loewi

Otto Loewi (03 June 1873 to 25 December 1961) was a German-born pharmacologist and psychobiologist who discovered the role of acetylcholine as an endogenous neurotransmitter. For his discovery he was awarded the Nobel Prize in Physiology or Medicine in 1936, which he shared with Sir Henry Dale, who was a lifelong friend that helped to inspire the neurotransmitter experiment. Loewi met Dale in 1902 when spending some months in Ernest Starling’s laboratory at University College, London.

GABA and Mental Disorders

Research Paper Title

Development and validation of a UPLC-MS/MS method for the simultaneous determination of gamma-aminobutyric acid and glutamic acid in human plasma.

Background

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 analyse GABA and glutamic acid in plasma.

Methods

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.

Results

Chromatographic separation was achieved on an Acquity UPLC HSS reversed phase C18 column using gradient elution. Analytes were detected using electrospray ionisation 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.

Conclusions

The reported method is well suited for the measurement of plasma GABA and glutamic acid in pre-clinical or clinical studies.

Reference

de Bie, T.H., Witkamp, R.F., Jongsma, M.A. & Balvers, M.G.J. (2021) Development and validation of a UPLC-MS/MS method for the simultaneous determination of gamma-aminobutyric acid and glutamic acid in human plasma. Journal of Chromatography. doi: 10.1016/j.jchromb.2020.122519. Online ahead of print.