A quantitative assay for 4‐hydroxybutyric acid was developed using D6‐4‐hydroxybutyric acid as an internal standard. 4‐Hydroxybutyric acid was isolated by liquid chromatography and the amount quantified by selected ion monitoring, ammonia chemical ionization gas chromatography/mass spectrometry of the trimethylsilyl derivatives. The concentrations of 4‐hydroxybutyric in control physiological fluids were: 2.64 ± 3.46 mmol mol−1 creatinine in urine, 1.09 ± 2.87 μmol l−1 in plasma, 0.98 ± 1.17 μmol l−1 in cerebrospinal fluid and 1.28 ± 0.47 μmol l−1 in amniotic fluid. The concentration of 4‐hydroxybutyric acid in the amniotic fluid from a pregnancy at risk for 4‐hydroxybutyric aciduria was 2.30 μmol l−1, indicating an unaffected fetus. The stable isotope dilution assay of 4‐hydroxybutyric acid in physiological fluid samples is a rapid, sensitive and accurate method for quantification, as well as a valuable technique for the prenatal diagnosis of 4‐hydroxybutyric aciduria.
ASJC Scopus subject areas
- Molecular Medicine