Planta Med 2006; 72(14): 1273-1278
DOI: 10.1055/s-2006-947241
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Inter-Species Variability of Haplamine Metabolism and Identification of its Phase I Metabolites from Liver Microsomes

Sompheary Ea1 , Sok-Siya Bun2 , Claude Aubert1 , Valentina Akhmedjanova4 , Evelyne Ollivier2 , Chhan Siv3 , Hot Bun1
  • 1Laboratory of Pharmacokinetics and Toxicokinetics, EA 3286, Faculty of Pharmacy, Marseille, France
  • 2Laboratory of Pharmacognosy, Faculty of Pharmacy, Marseille, France
  • 3Laboratory of Organo-Phosphorus UMR CNRS 6180, University of Paul Cézanne, Marseille, France
  • 4Uzbek Academy of Sciences, Yunusov Institute of the Chemistry of Plant Substances, Tashkent, Uzbekistan
Further Information

Publication History

Received: April 28, 2006

Accepted: July 25, 2006

Publication Date:
18 September 2006 (online)

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 µm) 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.

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Dr. Claude Aubert

Laboratory of Pharmacokinetics and Toxicokinetics

Faculty of Pharmacy

27 Bd Jean Moulin

13385 Marseille cedex 5

France

Phone: +33-4-91-83-55-09

Fax: +33-4-91-83-56-67

Email: claude.aubert@pharmacie.univ-mrs.fr