Quantitation of methylmalonic acid and other dicarboxylic acids in normal serum and urine using capillary gas chromatography-mass spectrometry

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Abstract

Methylmalonic acid, succinic acid, and other dicarboxylic acids have been extracted and partially purified from serum and urine using ether extraction and high-performance liquid chromatography. The t-butyldimethylsilyl derivatives were prepared and analyzed using capillary gas chromatography-mass spectrometry with selected ion monitoring. The addition of [methyl-2H3]methylmalonic acid and [1,4-13C2]succinic acid to the starting samples made it possible to quantitate these two dicarboxylic acids. Normal ranges for methylmalonic acid and succinic acid were determined in human and rat serum and in human urine. The utilization of other internal standards would make it possible to quantitate malonic, dimethylmalonic, ethylmalonic, methylsuccinic, glutaric, and other dicarboxylic acids.

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    This work was supported by Grant AM21365, awarded by the National Institute of Arthritis, Metabolism, and Digestive Diseases, DHEW, and Grant RR01152, awarded by the Division of Research Resources, NIH.

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