Stable isotope dilution analysis of 4-hydroxybutyric acid: an accurate method for quantification in physiological fluids and the prenatal diagnosis of 4-hydroxybutyric aciduria.
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 mumol l-1 in plasma, 0.98 +/- 1.17 mumol l-1 in cerebrospinal fluid and 1.28 +/- 0.47 mumol 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 mumol 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.
Kimberly H. Courtwright and Joseph W. Summers Metabolic Disease Center, Baylor University Medical Center, Dallas, Texas 75246.
K M
KM
Gibson
S
S
Aramaki
L
L
Sweetman
W L
WL
Nyhan
D C
DC
DeVivo
A K
AK
Hodson
C
C
Jakobs
D000138:Acidosis / Q000652:urine*; D000328:Adult; D000649:Amniocentesis; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006885:Hydroxybutyrates / Q000032:analysis*; D007202:Indicators and Reagents; D007223:Infant; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011865:Radioisotope Dilution Technique; D012978:Sodium Oxybate / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid
D006885:Hydroxybutyrates; D007202:Indicators and Reagents; D012978:Sodium Oxybate