Phase I metabolism of ganstigmine. Rat, dog, monkey and human liver microsomal extracts investigated by liquid chromatography electrospray tandem mass spectrometry

✍ Scribed by Catinella Silvia; Pelizzi Nicola; Puccini Paola; Marchetti Silvia; Zanol Margherita; Acerbi Daniela; Ventura Paolo

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 299 KB
• Volume: 36
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/jms.228

✦ Synopsis

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. Copyright © 2001 John Wiley & Sons, Ltd.