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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
- Source :
- Journal of pharmaceutical and biomedical analysis. 154
- Publication Year :
- 2017
-
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.
- Subjects :
- Sulfadoxine
medicine.medical_treatment
Clinical Biochemistry
Pharmaceutical Science
Amodiaquine
Lumefantrine
030226 pharmacology & pharmacy
01 natural sciences
Analytical Chemistry
03 medical and health sciences
chemistry.chemical_compound
Antimalarials
Plasma
0302 clinical medicine
Pharmacokinetics
Tandem Mass Spectrometry
Drug Discovery
Blood plasma
medicine
Humans
Artemether
Spectroscopy
Quinine
Fluorenes
Chromatography
Chemistry
Mefloquine
010401 analytical chemistry
Temperature
Reproducibility of Results
Artemisinins
3. Good health
0104 chemical sciences
Ethanolamines
Dried Blood Spot Testing
medicine.drug
Chromatography, Liquid
Subjects
Details
- ISSN :
- 1873264X
- Volume :
- 154
- Database :
- OpenAIRE
- Journal :
- Journal of pharmaceutical and biomedical analysis
- Accession number :
- edsair.doi.dedup.....abdd464802adfa7f60106528038da360