Development of a SPE/HPLC/DAD method for the determination of antileishmanial 2-substituted quinolines and metabolites in rat plasma

被引：3

作者：

Desrivot, Julie

Moussa, Fathi

Champy, Pierre

Fournet, Alain

Figadere, Bruno

Herrenknecht, Christine

机构：

[1] Univ Paris 11, Ctr Etud Pharmaceut, Lab Pharmacognosie, BioCIS UMR 8076, F-92290 Chatenay Malabry, France

[2] Univ Paris 11, Ctr Etud Pharmaceut, Lab Chimiotherapie Antiparasitaire, BioCIS UMR 8076, F-92290 Chatenay Malabry, France

[3] Univ Paris 11, Ctr Etud Pharmaceut, CNRS, UMR 8612, F-92290 Chatenay Malabry, France

[4] Univ Paris 11, Lab Pharmacognosie, IRD, US 084, F-92290 Chatenay Malabry, France

来源：

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2007年 / 854卷 / 1-2期

关键词：

leishmaniasis; solid phase extraction; 2-substituted quinoline; protein binding; lipophilicity; solubility;

D O I：

10.1016/j.jchromb.2007.04.029

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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,, lipophilicity and solubility were determined, as well as the extent of plasma protein or albumin binding. (C) 2007 Elsevier B.V. All rights reserved.

引用

页码：230 / 238

页数：9

共 26 条

[1] Pharmaceutical evaluation of early development candidates "the 100 mg-approach" [J].

Balbach, S ;

Korn, C .

INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2004, 275 (1-2) :1-12

[2] Decrease of intestinal P-glycoprotein activity by 2n-propylquinoline, a new oral treatment for visceral leishmaniasis [J].

Belliard, AM ;

Leroy, C ;

Banide, H ;

Farinotti, R ;

Lacour, B .

EXPERIMENTAL PARASITOLOGY, 2003, 103 (1-2) :51-56

[3] Determination of the human cytochrome P450s involved in the metabolism of 2n-propylquinoline [J].

Belliard, AM ;

Baune, B ;

Fakhfakh, M ;

Hocquemiller, R ;

Farinotti, R .

XENOBIOTICA, 2003, 33 (04) :341-355

[4] Determination of liquid-liquid partition coefficients by separation methods [J].

Berthod, A ;

Carda-Broch, S .

JOURNAL OF CHROMATOGRAPHY A, 2004, 1037 (1-2) :3-14

[5] Styrylquinolines, integrase inhibitors acting prior to integration:: a new mechanism of action for anti-integrase agents [J].

Bonnenfant, S ;

Thomas, CM ;

Vita, C ;

Subra, F ;

Deprez, E ;

Zouhiri, F ;

Desmaële, D ;

d'Angelo, J ;

Mouscadet, JF ;

Leh, H .

JOURNAL OF VIROLOGY, 2004, 78 (11) :5728-5736

[6] Binding of iralukast to serum proteins and erythrocytes:: measurements using ultrafiltration and an erythrocyte partitioning method [J].

Colussi, D ;

Parisot, C ;

Lefèvre, G .

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 1999, 7 (02) :167-173

[7] Metabolism of 2-substituted quinolines with antileishmanial activity studied in vitro with liver microsomes, hepatocytes and recombinantly expressed enzymes analyzed by LC/MS [J].

Desrivot, Julie ;

Edlund, Per-Olof ;

Svensson, Richard ;

Baranczewski, Pawel ;

Fournet, Alain ;

Figadere, Bruno ;

Herrenknecht, Christine .

TOXICOLOGY, 2007, 235 (1-2) :27-38

[8] Synthesis and biological evaluation of substituted quinolines:: Potential treatment of protozoal and retroviral co-infections [J].

Fakhfakh, MA ;

Fournet, A ;

Prina, E ;

Mouscadet, JF ;

Franck, X ;

Hocquemiller, R ;

Figadère, B .

BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (23) :5013-5023

[9] Substituted quinolines induce inhibition of proliferation of HTLV-1 infected cells [J].

Fournet, A ;

Mahieux, R ;

Fakhfakh, MA ;

Franck, X ;

Hocquemiller, R ;

Figadère, B .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (05) :891-894

[10] THE ACTIVITY OF 2-SUBSTITUTED QUINOLINE ALKALOIDS IN BALB/C MICE INFECTED WITH LEISHMANIA-DONOVANI [J].

FOURNET, A ;

GANTIER, JC ;

GAUTHERET, A ;

LEYSALLES, L ;

MUNOS, MH ;

MAYRARGUE, J ;

MOSKOWITZ, H ;

CAVE, A ;

HOCQUEMILLER, R .

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1994, 33 (03) :537-544

← 1 2 3 →