Determination of the R(-)- and S(+)-enantiomers of gamma-vinyl-gamma-aminobutyric acid in human body fluids by gas chromatography--mass spectrometry.

An analytical procedure, which allows the determination and quantitation of the R(-)- and S(+)-enantiomers of gamma-vinyl-gamma-aminobutyric acid (gamma-vinyl-GABA; MDL 71.754) in body fluids was developed. The method is based on a combined gas chromatographic--mass spectrometric technique. A glass capillary column coated with a chiral phase enabled the separation of the enantiomers of gamma-vinyl-GABA as their N-trifluoroacetyl-O-methyl ester derivatives. This was followed by quantitation using a selected ion monitoring technique in the electron-impact mode of ionization. The internal standard, gamma-acetylenic GABA, was included throughout the work-up of the samples. The assay was shown to be reproducible, specific and sensitive. No interferences were encountered from plasma, urine or cerebrospinal fluid constituents. The method was applied to the analysis of plasma samples obtained from a human volunteer who had received racemic gamma-vinyl-GABA. Significant differences in the plasma concentrations and plasma half-lives of the two enantiomers were seen, clearly illustrating the need for a specific assay technique capable of distinguishing between the enantiomers of this drug.