title: Studies on the Biotransformation of Veratric Acid, a Human Metabolite of Mebeverine, by Using the Incubated Hen's Egg.
abstract: Metabolism studies with selected test substances have shown that a model on the basis of the incubated hen's egg is suitable as a supplement to animal experimentation. Because of its 3,4-dimethoxyphenyl structure veratric acid (3,4-dimethoxybenzoic acid), a known human metabolite of mebeverine, was chosen as model substance for the present investigations and the parent compound as well as 4-hydroxy-3-methoxybenzoic acid were identified as main metabolites. The absence of 3-hydroxy-4-methoxybenzoic acid lets conclude that the O-demethylation takes place exclusively at the p-methoxyl function. In addition, 3,3',4,4'-tetramethoxy-l-ornithuric acid (2,5-bis-(3,4-dimethoxybenzoylamino)pentanoic acid) and its O-desmethyl derivative could be characterized as further metabolites. So far an amino acid conjugate has not been described after veratric acid administration in a vertebrate. There were no indications for the appearance of 3,4-dihydroxybenzoic acid in the veratric acid metabolism. This was confirmed by corresponding studies having the isomeric guaiacol acids as precursor. Furthermore, it could be proved that in ovo the O-methylation of 3,4-dihydroxybenzoic acid occurs regioselective at the m-hydroxyl group. The results which broaden the knowledge on the metabolic fate of veratric acid are discussed in comparison with those in mammals. The metabolites were identified by GC-MS, ESI-HRMS and LC/ESI-MS/MS. The structure of the synthesized reference substance was confirmed by MS, (1)H and (13)C NMR spectral data.
authors.affiliation: Private Laboratory, Brunow, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Kiep
authors.affiliation: Department of Organic Chemistry, Faculty of Biology, Chemistry and Earth Sciences, University of Bayreuth, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Göhl
authors.affiliation: Leibniz Institute of Plant Biochemistry, Halle, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schmidt
authors.affiliation: Department of Organic Chemistry, Faculty of Biology, Chemistry and Earth Sciences, University of Bayreuth, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Seifert
mesh_terms: D000586:Amination; D000818:Animals; D001711:Biotransformation; D002645:Chickens; D006139:Guaiacol / Q000031:analogs & derivatives / Q000378:metabolism; D008745:Methylation; D023421:Models, Animal; D010063:Ovum / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism*; D014641:Vanillic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D010627:Phenethylamines; C009333:veratric acid; D006139:Guaiacol; C005096:mebeverine; D014641:Vanillic Acid