title: In Vitro Metabolism Evaluation of the Ergot Alkaloid Dihydroergotamine: Application of Microsomal and Biomimetic Oxidative Model.
abstract: Dihydroergotamine is a semisynthetic natural product derived from ergotamine, an ergot alkaloid. It is used to treat migraines, a neurological disease characterized by recurrent moderate to severe headaches. In this work, thein vitrometabolism of dihydroergotamine was evaluated in a biomimetic phase I reaction, aiming to verify all possible formed metabolites. Dihydroergotamine was submitted to anin vitrometabolism assay using rat liver microsomes, and the metabolites were analyzed by HPLC-MS/MS. The biomimetic reactions were performed with Jacobsen catalyst for scaling up production of oxidized metabolites. Two hydroxylated metabolites were isolated and characterized by MS/MS and1H NMR analysis.
authors.affiliation: Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Anelize
authors.initials: A
authors.lastname: Bauermeister
authors.affiliation: Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Fernando Armani
authors.initials: FA
authors.lastname: Aguiar
authors.affiliation: Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Lucas Maciel Mauriz
authors.initials: LM
authors.lastname: Marques
authors.affiliation: Vita Nova, Hortolândia, São Paulo, Brazil.
authors.forename: Jose Dos Santos
authors.initials: JD
authors.lastname: Malta
authors.affiliation: Vita Nova, Hortolândia, São Paulo, Brazil.
authors.forename: Fábio
authors.initials: F
authors.lastname: Barros
authors.affiliation: Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Daniel Roberto
authors.initials: DR
authors.lastname: Callejon
authors.affiliation: Laboratório de Metabolismo In Vitro e Técnicas de Separação, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Anderson Rodrigo Moraes
authors.initials: AR
authors.lastname: de Oliveira
authors.affiliation: Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Norberto Peporine
authors.initials: NP
authors.lastname: Lopes
mesh_terms: D000818:Animals; D002723:Chlorobenzoates / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004087:Dihydroergotamine / Q000378:metabolism* / Q000493:pharmacokinetics*; D006801:Humans; D006900:Hydroxylation; D008658:Inactivation, Metabolic; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry
chemical_list: D002723:Chlorobenzoates; D004087:Dihydroergotamine; C000433:3-chloroperbenzoic acid