title: Inter-species variability of haplamine metabolism and identification of its phase I metabolites from liver microsomes.
abstract: Haplamine, a pyranoquinoline alkaloid, was isolated from the genus Haplophyllum. The inter-species variability of haplamine metabolism was determined by reversed phase high performance liquid chromatography (HPLC) with UV detection. Microsomes from the liver of rats, mice, rabbits, guinea-pigs and humans were incubated with haplamine. After incubation, samples were extracted with a mixture of ethyl acetate and isopropyl alcohol (90 : 10; v/v). Haplamine and its metabolites were separated by HPLC using Nucleosil C18 Nautilus (5 microm) connected with a precolumn of the same type. The HPLC mobile phase consisted of water (A) and a mixture of methanol and acetonitrile (85 : 15; v/v) (B) used in a gradient mode (17 to 27 % B for 10 min, 27 to 90 % B for 37 min, 90 to 17 % B for 3 min, and finally 17 % B for 3 min) at 1 mL/min. Quantitative and qualitative results showed significant inter-species differences in haplamine metabolism. Qualitative similarities were found between guinea-pigs, rabbits, and humans. The metabolites were isolated by HPLC and identified by GC/MS after silylation. The phase I metabolites identified in human liver microsomes were TRANS/CIS-3,4-dihydroxy-9-O-desmethylhaplamine, TRANS/CIS-3,4-dihydroxyhaplamine and 9-O-desmethylhaplamine.
authors.affiliation: Laboratory of Pharmacokinetics and Toxicokinetics, EA 3286, Faculty of Pharmacy, Marseille, France.
authors.forename: Sompheary
authors.initials: S
authors.lastname: Ea
authors.forename: Sok-Siya
authors.initials: SS
authors.lastname: Bun
authors.forename: Claude
authors.initials: C
authors.lastname: Aubert
authors.forename: Valentina
authors.initials: V
authors.lastname: Akhmedjanova
authors.forename: Evelyne
authors.initials: E
authors.lastname: Ollivier
authors.forename: Chhan
authors.initials: C
authors.lastname: Siv
authors.forename: Hot
authors.initials: H
authors.lastname: Bun
mesh_terms: D000700:Analgesics / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000378:metabolism*; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000493:pharmacokinetics*; D011714:Pyrans / Q000493:pharmacokinetics*; D015363:Quinolones / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D027821:Rutaceae; D013045:Species Specificity; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000700:Analgesics; D010936:Plant Extracts; D011714:Pyrans; D015363:Quinolones; C515941:haplamine