Desrivot Julie, Moussa Fathi, Champy Pierre, Fournet Alain, Figadère Bruno, Herrenknecht Christine
Centre d'Etudes Pharmaceutiques, Laboratoire de Pharmacognosie, BioCIS UMR 8076, Université Paris-Sud 11, 5 rue J-B Clément, 92290 Châtenay-Malabry, France.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jul 1;854(1-2):230-8. doi: 10.1016/j.jchromb.2007.04.029. Epub 2007 May 1.
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.
开发了一种固相萃取/高效液相色谱/二极管阵列检测法，用于在体内监测我们实验室正在研究的三种新型抗利什曼原虫的2-取代喹啉，以开发口服治疗药物。为优化该方法，本研究纳入了三种I期代谢物。在测试的四种吸附剂中，选择了三官能tC(18)柱（由三官能硅烷与硅胶表面反应制得）。开发了两种线性梯度以确保代谢物的分离。喹啉从大鼠血浆中的回收率在80.6%至88.2%之间。从药物开发的角度出发，测定了表观pK(a)、亲脂性和溶解度，以及血浆蛋白或白蛋白结合程度。
