Development of a SPE/HPLC/DAD method for the determination of antileishmanial 2-substituted quinolines and metabolites in rat plasma.
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.
Desrivot
Julie
J
Centre d'Etudes Pharmaceutiques, Laboratoire de Pharmacognosie, BioCIS UMR 8076, Université Paris-Sud 11, 5 rue J-B Clément, 92290 Châtenay-Malabry, France.
Moussa
Fathi
F
Champy
Pierre
P
Fournet
Alain
A
Figadère
Bruno
B
Herrenknecht
Christine
C
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
D000981:Antiprotozoal Agents; D011804:Quinolines