title: Phase I metabolism of ganstigmine. Rat, dog, monkey and human liver microsomal extracts investigated by liquid chromatography electrospray tandem mass spectrometry.
abstract: Ganstigmine, a new acetylcholinesterase inhibitor, was incubated with rat liver microsomes and the resulting metabolites were identified by high-performance liquid chromatographic/mass spectrometric (HPLC/MS) and HPLC/MS/MS analyses. The results showed the formation of eight main metabolites, among which geneseroline and molecules corresponding to mono-hydroxylated, demethylated and reduced ganstigmine. The metabolic profile drawn for humans, dog and monkey showed a pattern very similar to that of rat: only in the case of liver dog microsomes higher amounts of geneseroline and of a metabolite identified as demethylated and reduced drug were detected.
authors.affiliation: Chiesi Farmaceutici SpA, R&D, Analytical Chemistry and Pharmacokinetics Departments, Via Palermo 26/A, I-43100 Parma, Italy. s.catinella@chiesigroup.com
authors.forename: S
authors.initials: S
authors.lastname: Catinella
authors.forename: N
authors.initials: N
authors.lastname: Pelizzi
authors.forename: P
authors.initials: P
authors.lastname: Puccini
authors.forename: S
authors.initials: S
authors.lastname: Marchetti
authors.forename: M
authors.initials: M
authors.lastname: Zanol
authors.forename: D
authors.initials: D
authors.lastname: Acerbi
authors.forename: P
authors.initials: P
authors.lastname: Ventura
mesh_terms: D000470:Alkaloids / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D002219:Carbamates / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D006801:Humans; D006900:Hydroxylation; D008252:Macaca fascicularis; D008297:Male; D013058:Mass Spectrometry; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
chemical_list: D000470:Alkaloids; D002219:Carbamates; D002800:Cholinesterase Inhibitors; C447079:ganstigmine