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Clin Chim Acta. 2000 Feb 25;292(1-2):93-105.

Stereodifferentiation of 3-hydroxyisobutyric- and 3-aminoisobutyric acid in human urine by enantioselective multidimensional capillary gas chromatography-mass spectrometry.

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Department of Food Chemistry, J.W. Goethe-University Frankfurt/Main, Marie-Curie-Strasse 9, 60439, Frankfurt, Germany.


The chiral metabolites 3-hydroxyisobutyric acid (HIBA) and 3-aminoisobutyric acid (AIBA) are intermediates in the pathways of L-valine and thymine and play an important role in the diagnosis of the very rare inherited metabolic diseases 3-hydroxyisobutyric aciduria (McKusick 236975) and methylmalonic semialdehyde dehydrogenase deficiency (McKusick 603178-MSDD). Until now only a few approaches have been made in enantioselective analysis of HIBA and AIBA and for that reason very little information is available on enantiomeric ratios of these metabolites in man. This paper reports on the simultaneous stereodifferentiation of HIBA and AIBA in human urine as corresponding N(O)-methoxycarbonyl methyl esters by derivatization with methyl chloroformate (MCF) using enantioselective multidimensional gas chromatography-mass spectrometry (enantio-MDGC/MS) with heptakis-(2, 3-di-O-methyl-6-O-tert.-butyl-dimethylsilyl)-beta-cyclodextrin as the chiral stationary phase. During this investigation urine samples from different patients and healthy controls were analyzed in order to reveal characteristic enantiomeric patterns of these metabolites. A trend of dominating R-HIBA excretion in the control urine samples investigated was observed. An excretion of more than 80% S-HIBA was found in the urines of two patients with ketonemic vomiting. There are some clues indicating a possible renal reabsorbtion of S-HIBA similar to those of S-AIBA. Furthermore, there was a significant finding with regard to the enantiomeric distribution of AIBA in a patient with MSDD - a markedly increased excretion of the S-enantiomer in contrast to the other samples. Using the enantiomeric ratios of AIBA, a previously investigated case of benign methylmalonic aciduria (bMMA) could be excluded from the diagnosis of MSDD.

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