High throughput assay for the determination of lumefantrine in plasma

Annerberg, Anna; Singtoroj, Thida; Tipmanee, P.; White, Nicholas J.; Day, Nicholas P. J.; Lindegårdh, Niklas

doi:10.1016/j.jchromb.2005.06.022

Cited by 47 publications

(38 citation statements)

References 12 publications

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“…Plasma was separated and stored at -30°C until it was analysed with a validated highperformance liquid chromatography method. 23 The primary effi cacy endpoint was the proportion of patients with PCR-corrected adequate clinical and parasitological response (ACPR) at day 42-cure is defi ned as ACPR. The secondary effi cacy endpoint was PCR-uncorrected ACPR on day 42 or delivery (whichever came last) to account for placental sequestration of malaria parasites.…”

Section: Methodsmentioning

confidence: 99%

Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial

Piola¹,

Nabasumba²,

Turyakira³

et al. 2010

The Lancet Infectious Diseases

168

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Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial MSF Field Research SummaryBackground Malaria in pregnancy is associated with maternal and fetal morbidity and mortality. In 2006, WHO recommended use of artemisinin-based combination treatments during the second or third trimesters, but data on effi cacy and safety in Africa were scarce. We aimed to assess whether artemether-lumefantrine was at least as effi cacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara, Uganda. MethodsWe did an open-label, randomised, non-inferiority trial between October, 2006, and May, 2009, at the antenatal clinics of the Mbarara University of Science and Technology Hospital in Uganda. Pregnant women were randomly assigned (1:1) by computer generated sequence to receive either quinine hydrochloride or artemetherlumefantrine, and were followed up weekly until delivery. Our primary endpoint was cure rate at day 42, confi rmed by PCR. The non-inferiority margin was a diff erence in cure rate of 5%. Analysis of effi cacy was for all randomised patients without study deviations that could have aff ected the effi cacy outcome. This study was registered with ClinicalTrials.gov, number NCT00495508.Findings 304 women were randomly assigned, 152 to each treatment group. By day 42, 16 patients were lost to followup and 25 were excluded from the analysis. At day 42, 137 (99·3%) of 138 patients taking artemether-lumefantrine and 122 (97·6%) of 125 taking quinine were cured-diff erence 1·7% (lower limit of 95% CI -0·9). There were 290 adverse events in the quinine group and 141 in the artemether-lumefantrine group.Interpretation Artemisinin derivatives are not inferior to oral quinine for the treatment of uncomplicated malaria in pregnancy and might be preferable on the basis of safety and effi cacy.Funding Médecins Sans Frontières and the European Commission.

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Section: Methodsmentioning

confidence: 99%

Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial

Piola¹,

Nabasumba²,

Turyakira³

et al. 2010

The Lancet Infectious Diseases

168

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“…Stock solutions of CQ, AQ and MAQ were diluted in distilled water; MQ and DHA were diluted in methanol. LUM was diluted in acid methanol (methanol: acetic acid 99.8 mL + 0.2 mL) (Annerberg et al 2005). Seven serial dilutions (in RPMI 1640, 1:2) for each drug were pipetted into the wells and the plates were left to dry under sterile conditions.…”

Section: Study Population -Patients Visiting the Ismael Roldanmentioning

confidence: 99%

Sentinel network for monitoring in vitro susceptibility of Plasmodium falciparum to antimalarial drugs in Colombia: a proof of concept

Aponte

Díaz

Pava

et al. 2011

Mem. Inst. Oswaldo Cruz

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“…À notre connaissance, aucune défécation à l'acide n'a été décrite pour le dosage de la LF sur spot [13,14]. Seule une défécation douce à l'acétonitrile [9,10] ou au mé-thanol [14] ont été rapportées, respectivement pour les dosages plasmatiques et sur spot de sang total. Ces méthodes de défé-cation ne nous sont pas apparues suffisamment efficaces dans le cas des spots de sang séché.…”

Section: éTude De Faisabilité Chez L'enfantunclassified

“…Nos rendements d'extraction supérieurs à ceux décrits [13,14] pourraient s'expliquer par notre méthode de défécation plus drastique et par la double extraction liquide-liquide. La plupart des méthodes récemment développées utilise comme étalon interne des dérivés de la luméfantrine [10,13] développés par Novartis ou une autre molécule anti-paludique, comme l'halofantrine [14]. Nous n'avons pas pu nous procurer les dérivés de la luméfantrine.…”

Section: éTude De Faisabilité Chez L'enfantunclassified

“…De nombreuses méthodes de dosages d'antipaludéens sur SSS ont été développées au cours de ces dernières années [6][7][8]. L'étude de la littérature rapporte pour la luméfantrine plusieurs méthodes de dosages chromatographiques sur plasma [9][10][11] ou sur sang total [12]. Récem-ment, deux méthodes de dosage sur spot de sang séché ont été rapportées, permettant soit le dosage de la luméfantrine seule [13], soit de la molécule mère et de son métabolite [14].…”

Section: Introductionunclassified

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Dosage par chromatographie liquide haute performance de la luméfantrine sur spot de sang séché

et al. 2009

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Résumé -Objectif : La luméfantrine, est un nouvel antipaludéen de synthèse utilisé en association avec l'artéméter dans le traitement de l'accès palustre simple chez l'enfant. Sa mauvaise biodisponibilité impose un suivi des concentrations circulantes pour identifier les échecs thérapeutiques qui sont dus à une mauvaise absorption de ceux qui résultent d'un phénomène de résistance. Nous avons développé le dosage de la luméfantrine sur spot de sang séché, support adapté au prélèvement et au stockage des échantillons dans des conditions difficiles. Méthodes : Le dosage de la luméfantrine a été réalisé par chromatographie liquide après extraction liquide-liquide des spots par le mélange acétate d'éthyle/acide acétique. La séparation est réalisée sur colonne Xbridge avec une phase acétate d'ammonium pH 4 / acétonitrile (10/90 v/v) en mode isocratique. La détection est réalisée en UV à 335 nm, avec le tocol comme étalon interne. Résultats : La luméfantrine et l'étalon interne sont élués en respectivement 7,1 et 10,3 minutes. La méthode est linéaire entre 250 et 5000 µg/L. La limite de détection est de 85 µg/L avec une limite de quantification à 250 µg/L. La précision est satisfaisante (< 10 %), de même que l'exactitude (biais < 10 %). Les spots sont stables à +4 • C pendant 10 jours, mais une conservation à +25 • C, s'accompagne d'une baisse significative des concentrations. Les concentrations résiduelles chez des enfants traités 3 jours par la luméfantrine sont de 490 ±152 µg/L. Conclusion : Nous rapportons une méthode robuste et fiable de dosage de la luméfantrine sur spots de sang séché applicable aux études pharmacocinétiques et épidémiologiques. Mots clés : Luméfantrine, CLHP, spot de sang séchéAbstract -Aim: Lumefantrine is a new anti-malarial drug used in association with artemeter in the treatment of uncomplicated Plasmodium falciparum malaria in children. Poor absorption of lumefantrine needs to monitor concentrations to identify the nature of the therapeutic failure. We have developed the determination of lumefantrine on dried blood spots, which are frequently used to collect and store blood in hard conditions. Methods: Lumefantrine measurement was assayed by liquid chromatography after liquid-liquid extraction procedure using ethyl acetate/acetic acid as solvent. Separation was performed on a Xbridge column using ammonium acetate pH 4 / acetonitrile (10/90 v/v) in isocratic mode. UV detection was set at 335 nm using tocol as internal standard. Results: Lumefantrine and internal standard are eluted at 7.1 and 10.3 min, respectively. The method is linear from 250 to 5000 µg/L with a good sensitivity corresponding to 85 µg/L for limit of detection and 250 µg/L as limit of quantification. Precision (below 10%) and accuracy (below 10%) are satisfying. Lumefantrine concentrations were stable in dried blood spot during 10 days at +4 • C but a significant decrease was observed at +25 • C. Blood residual concentrations in children treated by lumefantrine during 3 days were 490 ±152 µg/L. Conclusion: We have develop...

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High throughput assay for the determination of lumefantrine in plasma

Cited by 47 publications

References 12 publications

Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial

Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial

Sentinel network for monitoring in vitro susceptibility of Plasmodium falciparum to antimalarial drugs in Colombia: a proof of concept

Dosage par chromatographie liquide haute performance de la luméfantrine sur spot de sang séché

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