A newborn screening approach to diagnose 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is a rare autosomal recessively inherited metabolic disorder. Patients suffer from avoidable neurologically devastating metabolic decompensations and thus would benefit from newborn screening (NBS). The diagnosis is currently made by measuring dry blood spot acylcarnitines (C5OH and C6DC) followed by urinary organic acid profiling for the differential diagnosis from several other disorders.

Urease-immobilized magnetic microparticles in urine sample preparation for metabolomic analysis by gas chromatography-mass spectrometry.

Urea, as an end product of protein metabolism and an abundant polar compound, significantly complicates the metabolomic analysis of urine by GC-MS. We developed a sample preparation method removing urea from urine samples prior the GC-MS analysis. The method based on urease immobilized on magnetic microparticles was compared with the others that are conventionally used (liquid-liquid extraction, free urease protocol), and samples without any treatment.

Impact of sample dimensionality on orthogonality metrics in comprehensive two-dimensional separations.

Orthogonality is a key parameter in the evaluation of the performance of a 2D chromatography-based separation system. Two different perspectives on orthogonality are determined: the extent of the separation space utilized (global orthogonality) and the uniformity of the coverage of the separation space (local orthogonality). This work aims to elucidate the impact of sample dimensionality (the number of separation processes involved) on orthogonality evaluation through the use of descriptors from seven different algorithms utilizing mutually different properties of a chromatogram: Pearson correlation, conditional entropy, asterisk equations, convex hull, arithmetic mean (AN) and harmonic mean of the nearest neighbor, and geometric surface coverage (SC).

Sample-independent approach to normalize two-dimensional data for orthogonality evaluation using whole separation space scaling.

Orthogonality is a key parameter that is used to evaluate the separation power of chromatography-based two-dimensional systems. It is necessary to scale the separation data before the assessment of the orthogonality. Current scaling approaches are sample-dependent, and the extent of the retention space that is converted into a normalized retention space is set according to the retention times of the first and last analytes contained in a unique sample to elute.