edoc

LC-MS/MS method for the simultaneous analysis of seven antimalarials and two active metabolites in dried blood spots for applications in field trials : analytical and clinical validation

Gallay, Joanna and Prod'hom, Sylvain and Mercier, Thomas and Bardinet, Carine and Spaggiari, Dany and Pothin, Emilie and Buclin, Thierry and Genton, Blaise and Decosterd, Laurent Arthur. (2018) LC-MS/MS method for the simultaneous analysis of seven antimalarials and two active metabolites in dried blood spots for applications in field trials : analytical and clinical validation. Journal of Pharmaceutical and Biomedical Analysis, 154. pp. 263-277.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/64801/

Downloads: Statistics Overview

Abstract

In epidemiological studies, antimalarials measurements in blood represent the best available marker of drugs exposure at population level, an important driver for the emergence of drug resistance. We have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for the simultaneous quantification of 7 frequently used antimalarials (amodiaquine, chloroquine, quinine, sulfadoxine, pyrimethamine, mefloquine, lumefantrine) and 2 active metabolites (N-desethyl-amodiaquine, desbutyl-lumefantrine) in 10-μl dried blood spots (DBS). This sampling approach is suitable for field studies wherein blood samples processing, transportation and storage are problematic. Sample preparation included extraction from a 3 mm-disk punched out of the DBS with 100-μl of methanol + 1% formic acid containing deuterated internal standards for all drugs. Good performances were achieved in terms of trueness (-12.1 to +11.1%), precision (1.4-15.0%) and sensitivity, with lower limits of quantification comprised between 2 ng/ml (sulfadoxine) and 20 ng/ml (chloroquine, quinine, pyrimethamine, mefloquine, lumefantrine and desbutyl-lumefantrine). All analytes were stable in DBS kept for 24 h at room temperature and at 37 °C. The developed assay was applied within the frame of a pharmacokinetic study including 16 healthy volunteers who received a single dose of artemether-lumefantrine. Lumefantrine concentrations in plasma and in DBS were highly correlated (R = 0.97) at all time points, confirming the assumption that lumefantrine concentrations determined in DBS confidently reflect blood concentrations. The blood/plasma ratio of 0.56 obtained using the Bland-Altman approach (and corresponding to the slope of the linear regression) is in line with very low penetration of lumefantrine into red blood cells. This sensitive multiplex LC-MS/MS assay enabling the simultaneous analysis of antimalarials in DBS is suitable for epidemiological studies in field conditions.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Health Interventions > Clinical Epidemiology (Genton)
UniBasel Contributors:Pothin, Emilie and Genton, Blaise
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0731-7085
e-ISSN:1873-264X
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:03 Jul 2018 10:58
Deposited On:03 Jul 2018 10:58

Repository Staff Only: item control page