GABA, GHB, and Homocarnosine

γ-Aminobutyric acid (4-aminobutyric acid, GABA), γ-hydroxybutyric acid (4-hydroxybutyric acid, GHB), and homocarnosine (γ-aminobutyryl-L-histidine) represent bioactive metabolites with diverse roles in intermediary metabolism and central neurotransmission. These metabolites have been shown to be increased in cerebrospinal fluid (CSF) and plasma in patients with several inheritable neurometabolic disorders. These include succinate semialdehyde dehydrogenase deficiency (also known as gamma-hydroxybutyric aciduria), GABA-transaminase deficiency, homocarnosinosis, hyper-β-alaninemia, and a putative combined semialdehyde dehydrogenase deficiency. The current chapter describes highly sensitive, quantitative methodologies for the determination of GABA and homocarnosine in CSF and GHB in plasma, with the potential for adaptation to other physiological fluids. GABA and GHB are quantified underivatized employing stable isotope dilution liquid chromatography-mass spectrometry. Conversely, homocarnosine is quantified as the butyl derivative utilizing isotope dilution liquid chromatography-tandem mass spectrometry.