title: Chiral liquid chromatography tandem mass spectrometry in the determination of the configuration of 2-hydroxyglutaric acid in urine.
abstract: D-2-Hydroxyglutaric aciduria and L-2-hydroxyglutaric aciduria are two distinct inherited metabolic diseases. The accurate diagnosis of the exact disorder relies on the determination of the configuration of the enantiomers, either D-2-hydroxyglutaric acid or L-2-hydroxyglutaric acid excreted in excess in urine of patients. The enantiomeric chiral separation of 2-hydroxyglutaric acid was achieved using a ristocetin A glycopeptide antibiotic silica gel bonded column. The chiral column was interfaced with a tandem mass spectrometer for the purpose of specifically detecting the eluting 2-hydroxyglutaric acid. Tandem mass spectrometry was employed using an electrospray ion source in the negative ion mode. Three parent-to-daughter transitions under collision-induced dissociation conditions were used to detect only 2-hydroxyglutaric acid. The two forms of the compound were satisfactorily separated with almost baseline resolution at 4.95 and 5.5 min. Three known patients with 2-hydroxyglutaric aciduria were identified to have L-2-hydroxyglutaric aciduria. The method is simple, selective, rapid, and free from interference.
authors.affiliation: Metabolic Screening Laboratory, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia. rashed@kfshrc.edu.sa
authors.forename: M S
authors.initials: MS
authors.lastname: Rashed
authors.forename: M
authors.initials: M
authors.lastname: AlAmoudi
authors.forename: H Y
authors.initials: HY
authors.lastname: Aboul-Enein
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D005977:Glutarates / Q000652:urine*; D006801:Humans; D013058:Mass Spectrometry; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D005977:Glutarates; C019417:alpha-hydroxyglutarate