Separation and quantification of the urinary enantiomers of 2‐hydroxyglutaric acid by capillary electrophoresis with capacitively coupled contactless conductivity detection: Application to the diagnosis of D‐ and L‐2‐hydroxyglutaric aciduria

Abstract

2-hydroxyglutaric aciduria is an inherited neurometabolic disorder with two major types: D-2-hydroxyglutaric aciduria and L-2-hydroxyglutaric aciduria. An easy and fast capillary electrophoresis system combined with a capacitively coupled contactless conductivity detection method was developed for the enantioseparation and determination of D-and L-2-hydroxyglutaric acid in urine. Dand L-2-hydroxyglutaric acids were separated using vancomycin as the chiral selector. The optimal separation conditions for enantiomers were achieved by the use of a buffer containing 50 mM 4-(N-morpholino) butane sulfonic acid solution (pH 6.5), an electroosmotic flow modifier (0.001% [w/v] polybrene), and 30 mM vancomycin as chiral selector. The analysis time was 6 min under optimal conditions. The optimized and validated method was successfully implemented for quantifying D-and L-2-hydroxyglutaric aciduria in patients' urine, without any pretreatment step. The linearity of the method was determined to be in the range of 2-100 mg/L for D-and L-2-hydroxyglutaric acid in urine. The precision (relative standard deviation%) was obtained at about 7%. For D-and L-2-hydroxyglutaric acids, the limits of detection were 0.567 and 0.497 mg/L, respectively.

Focal dystonia in an adult with L-2- hydroxyglutaric aciduria

“…The mutation detected in our patient is a null mutation (DNA variant c.1003C > T, protein variant p.[Arg335*]), which is a known previously reported mutation. 6 …”

“… 5 The clinical and radiological findings of L-2-HGA are confirmed by targeted L-2-HGH and L-2-HGA sequencing to identify the pathological mutation. 6 …”

Determination of organic acids for predicting sourness intensity of tea beverage by liquid chromatography–tandem mass spectrometry and chemometrics methods

“…Methods have been developed for determining OAs using separation techniques (e.g., capillary electrophoresis, gas chromatography, and liquid chromatography [LC]) combined with different detection techniques such as refractive index, conductivity, electrochemical, spectrophotometric, or mass spectrometry (MS) detection [6–12]. Ultra‐high‐performance LC coupled with tandem MS (UHPLC‐MS/MS) is a leading technique due to its excellent performance in sensitivity, selectivity, throughput, and reproducibility.…”