title: Development of a SPE/HPLC/DAD method for the determination of antileishmanial 2-substituted quinolines and metabolites in rat plasma.
abstract: A SPE/HPLC/DAD method was developed for the in vivo monitoring of three new antileishmanial 2-substituted quinolines under study in our laboratory for the development of an oral treatment. Three phase I metabolites were included in this work for the optimization of the method. Trifunctional tC(18) cartridges (resulting from the reaction of trifunctional silanes with silica surface) were selected among four sorbents tested. Two linear gradients were developed to ensure resolution of metabolites. Recovery of quinolines from rat plasma was comprised between 80.6 and 88.2%. In a drug development perspective, apparent pK(a), lipophilicity and solubility were determined, as well as the extent of plasma protein or albumin binding.
authors.affiliation: Centre d'Etudes Pharmaceutiques, Laboratoire de Pharmacognosie, BioCIS UMR 8076, Université Paris-Sud 11, 5 rue J-B Clément, 92290 Châtenay-Malabry, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Desrivot
authors.forename: Fathi
authors.initials: F
authors.lastname: Moussa
authors.forename: Pierre
authors.initials: P
authors.lastname: Champy
authors.forename: Alain
authors.initials: A
authors.lastname: Fournet
authors.forename: Bruno
authors.initials: B
authors.lastname: Figadère
authors.forename: Christine
authors.initials: C
authors.lastname: Herrenknecht
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000097:blood* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007891:Leishmania / Q000187:drug effects*; D008297:Male; D011485:Protein Binding; D011804:Quinolines / Q000097:blood* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D014462:Ultrafiltration
chemical_list: D000981:Antiprotozoal Agents; D011804:Quinolines