title: Analysis of 3-hydroxydodecanedioic acid for studies of fatty acid metabolic disorders: preparation of stable isotope standards.
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.
authors.affiliation: Department of Chemistry, University of Missouri-St. Louis, Missouri.
authors.forename: J S
authors.initials: JS
authors.lastname: Chickos
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Way
authors.forename: J
authors.initials: J
authors.lastname: Wilson
authors.forename: M
authors.initials: M
authors.lastname: Shaharuzzaman
authors.forename: J
authors.initials: J
authors.lastname: Laird
authors.forename: M
authors.initials: M
authors.lastname: Landt
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000652:urine; D005227:Fatty Acids / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods / Q000592:standards; D006801:Humans; D007554:Isotopes / Q000592:standards; D007850:Lauric Acids / Q000652:urine*; D008052:Lipid Metabolism, Inborn Errors / Q000652:urine*; D012015:Reference Standards
chemical_list: D005227:Fatty Acids; D007554:Isotopes; D007850:Lauric Acids; C022145:3-hydroxydodecanoic acid; D015094:3-Hydroxyacyl CoA Dehydrogenases