STABLE-ISOTOPE DILUTION ANALYSIS OF GABA IN CSF USING SIMPLE SOLVENT-EXTRACTION AND ELECTRON-CAPTURE NEGATIVE-ION MASS FRAGMENTOGRAPHY

GABA plays an important role in various neurological and mental disorders, in which elevated as well as decreased concentrations of GABA in CSF may occur (Jaeken et al 1990; Jakobs et al 1993). Most methods for determining GABA in brain tissue lack the sensitivity and specificity for measuring the low, free GABA levels in CSF. Three methods have been used to quantitate CSF free GABA: ion-exchange or reversed-phase liquid chromatography with fluorescence detection (Goldsmith et al 1987; Carchon et al 1991); gas chromatography-mass spectrometry, requiring laborious column extraction (Huizinga et al 1978); and radioreceptor assay (Enna et al 1977). The last method is non-specific and thus unreliable. We have developed a sensitive, selective and accurate stable isotope dilution GC-MS assay using a simple extraction procedure and electron-capture negative ionization (ECNI) mass fragmentographic detection. The method was applied to CSF samples of a patient suffering from succinic semialdehyde dehydrogenase (SSAD) deficiency (McKusick 271980) before and during Vigabatrin treatment.