NMR and HPLC-MS/MS analysis of synthetically prepared linoleic acid diol glucuronides.
Hydroxylated fatty acids are important mediators of many physiological and pathophysiological processes in a variety of human tissues. Recent evidence shows that in humans many of these are ultimately excreted in the urine as the glucuronide conjugates. In this paper we describe a general approach for the chemical synthesis of glucuronide conjugate derivatives of fatty acids. The synthesis strategy employs three steps (epoxidation, hydrolysis and glucuronidation) using methyl linoleate as a model non-hydroxylated starting compound. Hydroxylated starting compounds would require only the glucuronidation step. NMR and HPLC-MS/MS experiments were used to help determine the structure of the synthesized glucuronide conjugates and to identify fragmentation product ions useful for discriminating positional isomers in biological samples. This synthetic strategy should prove useful for generating analytical standards in order to identify and quantify glucuronide metabolites of hydroxylated fatty acids in humans.
Yang
Jie
J
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
Morton
Martha D
MD
Hill
Dennis W
DW
Grant
David F
DF
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D020719:Glucuronides / Q000138:chemical synthesis / Q000737:chemistry; D008041:Linoleic Acids / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry
D020719:Glucuronides; D008041:Linoleic Acids; D013256:Steroids