Epigalantamine

High-performance liquid chromatographic method with UV photodiode-array, fluorescence and mass spectrometric detection for simultaneous determination of galantamine and its phase I metabolites in biological samples.[Pubmed:17416214]

J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jun 15;853(1-2):265-74.

Galantamine, an alkaloid isolated from the bulbs and flowers of Caucasian snowdrop (Galanthus woronowii, Amaryllidaceae) and related species, is employed in human medicine for the treatment of various neuromuscular and neurodegenerative diseases. After the administration, the products of oxidative biotransformation (O-desmethyl-galantamine, N-desmethyl-galantamine, galantamine-N-oxide) and chiral conversion (Epigalantamine) are formed in various concentrations from parent compound. For the identification and determination of galantamine and its phase I metabolites in blood plasma and tissues, a new bioanalytical method based on a reversed-phase high-performance liquid chromatography with UV photodiode-array, fluorescence and mass spectrometric detection was developed, validated and applied to pharmacokinetic and biotransformation studies. Sample preparation included a homogenization of the rat tissues (liver, brain, hypophysis) in a phosphate buffer 0.05 mol/L pH 7.4. Plasma samples and tissue homogenates were purified using a mixed-mode solid-phase extraction (Waters Oasis MCX cartridges). Galantamine, its above-mentioned metabolites and the internal standard codeine were separated on a Discovery HS F5 column (Supelco, 150 mmx4.6 mm I.D., 5 microm) at flow rate of 1 mL/min using a linear gradient elution. UV photodiode-array and mass spectrometric detection were employed for the identification of individual galantamine metabolites in various biomatrices, the fluorescence detection (lambdaexcit=280 nm/lambdaemiss=310 nm) was chosen for the quantification of galantamine and its metabolites. The developed method was applicable in liver tissue in the range from 0.50 to 63.47 nmol/g of galantamine, from 0.32 to 41.42 nmol/g of O-desmethyl-galantamine, from 0.54 to 69.40 nmol/g of N-desmethyl-galantamine and from 0.70 to 89.03 nmol/g of Epigalantamine. Limit of detection was found to be 0.04 nmol/g for galantamine, 0.19 nmol/g for O-desmethyl-galantamine, and 0.07 nmol/g for N-desmethyl-galantamine and Epigalantamine.

In vitro metabolism of galanthamine hydrobromide (Nivalin) by rat and rabbit liver homogenate.[Pubmed:3609070]

Eur J Drug Metab Pharmacokinet. 1987 Jan-Mar;12(1):25-30.

The metabolism of galanthamine hydrobromide (Nivalin) was investigated in rat and rabbit liver homogenates. Experiments were carried out varying several parameters of incubation: substrate (galanthamine hydrobromide, galanthamine, galanthaminone and epigalanthamine), cofactor enrichment (NADPH, NADP/G-6-P, NAD), pH (7.4 and 9.3), time of incubation. Substrates and metabolites were identified and quantitatively determined by GC/MS. In vitro metabolism in rat liver homogenate was negligible. The experiments with rabbit liver homogenate indicated, that galanthamine was actively metabolised the major metabolites being the oxidised product - galanthaminone, and the isomer of galanthamine - Epigalantamine. The experimental results show that the metabolism of galanthamine is substrate and product stereoselective.