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, the in vitro metabolism of dihydroergotamine was evaluated in a biomimetic phase I reaction, aiming to verify all possible formed metabolites. Dihydroergotamine was submitted to an in vitro metabolism 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 and 1H NMR analysis.
Georg Thieme Verlag KG Stuttgart · New York.