Journal of Clinical Laboratory Analysis 2002-01-01

Analysis of 3-hydroxydodecanedioic acid for studies of fatty acid metabolic disorders: preparation of stable isotope standards.

J S Chickos, Barbara A Way, J Wilson, M Shaharuzzaman, J Laird, M Landt

Index: J. Clin. Lab Anal. 16(2) , 115-20, (2002)

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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.Copyright 2002 Wiley-Liss, Inc.