Abstract
Current diagnostic tests to detect disorders of fatty acids metabolism, such as long‐chain hydroxyacyl CoA dehydrogenase deficiency (LCHAD), are hampered by insensitivity or a long delay time required for results. Children with LCHAD deficiency are known to excrete 3‐hydroxydicarboxylic acids with chain lengths of 10–16 carbons, but a quantitative method to measure excretion of these potentially diagnostically important compounds has not been reported. We report synthetic schemes for synthesis of 3‐hydroxydodecanedioic acid and a di‐deuterated analog, suitable for use in a stable‐isotope dilution mass spectrometric analytical approach. Evaluation of several common derivatization protocols to produce a volatile derivative for gas chromatography determined that trimethylsyl derivatives produced the best efficiency and stability. Positive‐ion chemical ionization mass spectrometry provided the greatest yield of characteristic ions. These results indicate the basic reagents needed to develop sensitive and accurate 3‐hydroxydodecanedioic acid measurements for diagnosis of LCHAD deficiency and other fatty acid oxidation disorders. J. Clin. Lab. Anal. 16:115–120, 2002. © 2002 Wiley‐Liss, Inc.
Keywords: metabolic genetic disease, mass spectroscopy, diagnosis
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