Simultaneous determination of artemether and lumefantrine in fixed dose combination tablets by HPLC with UV detection

César, Isabela Costa; Nogueira, Francisco Cézar Costa; Pianetti, Gérson Antônio

doi:10.1016/j.jpba.2008.05.022

Cited by 43 publications

(27 citation statements)

References 13 publications

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“…1,2 Global malaria surveillance systems are believed to detect only 10% of the estimated global number of cases. 1 The spread and increase of parasite resistance to antimalarials poses a great challenge to malaria control, 3 and the limited number of antimalarials against Plasmodium falciparum has led to increasing difficulties in the development of drug policies and adequate disease management. 4 The situation is further compounded by counterfeit and substandard drugs, which form 10% of global medicines trade, 5 and 35% of all antimalarials in southeast Asia and sub-Saharan Africa are substandard.…”

Section: Introductionmentioning

confidence: 99%

“…Some studies have reported methods for the quantification of only artemether 8,9 or lumefantrine 10,11 in pharmaceutical and biological matrices. A few methods have been published for the simultaneous determination of artemether and lumefantrine in biological 3,12 and drug formulation matrices. 10,11 In 2011, Cesar and others 13 improved a method developed by Hodel and others 12 using liquid chromatography tandem mass spectrometry for the simultaneous quantification of artemether and lumefantrine of 14 antimalarials in human plasma, by eliminating a sample drying step and reducing the total chromatogram run time.…”

Section: Introductionmentioning

confidence: 99%

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Artemether–Lumefantrine Concentrations in Tablets and Powders from Ghana Measured by a New High-Performance Liquid Chromatography Method

Debrah

Nettey

Miltersen

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. We developed and validated a new analytical method for the simultaneous quantification of artemether and lumefantrine in fixed-dose tablets and powders for reconstitution into pediatric suspensions (PSs). The method showed linearity (r 2 > 0.9947), precision (coefficient of variation < 2%), accuracy (deviation of mean from actual concentrations < 4%), and specificity (peak purities > 99%). The validated method was used to analyze 24 batches of fixed-dose tablets and PSs of artemether and lumefantrine. Of the samples, 23 were obtained using convenience sampling of commonly available brands within Accra in Ghana and one was obtained from Aarhus University Hospital. In all, 83.3% (confidence interval: 80-120%) passed for both artemether and lumefantrine contents, 16.7% failed by the U.S. Pharmacopoeia standards, 8.3% failed for one content, and 8.3% failed for both contents. All four products (16.7%) that failed were PSs, and two (8.3%) showed higher levels of artemether than prescribed (222% and 756%).

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Artemether–Lumefantrine Concentrations in Tablets and Powders from Ghana Measured by a New High-Performance Liquid Chromatography Method

Debrah

Nettey

Miltersen

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…Chromatographic methods for the analysis of artemether and lumefantrine have been reported, focusing on the quantitation of these drugs in pharmaceutical products 7 or biological matrices. 8,9 HPLC with UV detection is the most common analytical method employed for lumefantrine, 10,11 whereas for artemether, electrochemical 12,13 or ultraviolet detection after acid hydrolysis 14 have been reported.…”

Section: Introductionmentioning

confidence: 99%

Electrospray ionization tandem mass spectrometry of the two main antimalarial drugs: artemether and lumefantrine

Santos¹,

Alves²,

Eberlin³

et al. 2012

J. Braz. Chem. Soc.

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Ionização por electrospray no modo de íons positivos, e espectrometria de massas de alta resolução e exatidão, e em tandem, realizadas em espectrômetro de massas híbrido quadrupolo e tempo de vôo, foram utilizadas para investigar a dissociação química das moléculas intactas dos dois antimaláricos mais amplamente utilizados: artemeter e lumefantrina. As rotas de dissociação das formas cationizadas e protonadas foram claramente estabelecidas via determinações de massas de alta resolução e distribuição isotópica. Os resultados obtidos podem auxiliar a monitorização e a quantificação de artemeter e lumefantrina por LC-MS/MS, assim como de novos derivados ou outros fármacos antimaláricos estruturalmente relacionados.Electrospray ionization in the positive ion mode and high resolution and high accuracy tandem mass spectrometry performed in a hybrid quadrupole time-of-flight mass spectrometer were used to investigate the dissociation chemistry of the intact molecules of two most widely used antimalarial drugs: artemether and lumefantrine. The dissociation pathways of their cationized and protonated forms were rationalized based on high accuracy mass measurements and isotopic distributions. The obtained results should benefit LC-MS/MS monitoring and quantitation by mass spectrometry of the artemether and lumefantrine molecules, as well as of new derivatives or other structurally related antimalarial drugs. Keywords: artemether, lumefantrine, ion dissociation, tandem mass spectrometry, ESI-MS/MS IntroductionArtemether-lumefantrine is a drug association currently of wide use for malaria treatment. The registered fixed dose combination is commercialized in tablets that contain 20 mg of artemether and 120 mg of lumefantrine. 1 The World Health Organization (WHO) recommends this association as first line therapy for falciparum malaria in endemic areas, mainly when cases of resistance against traditional drugs are reported. 2 Artemether (Scheme 1) is a semisynthetic derivative of artemisinin, a natural product of the Chinese herb Artemisia annua, 3 whereas lumefantrine (Scheme 1) is a synthetic racemic fluorene derivative originally named benflumetol. 4 Counterfeiting or drugs with substandard antimalarial doses are however major problems of worldwide occurrence that dramatically affects the efficacy of malarial treatment. Ineffective or poor quality drugs is of great concern since their use may contribute to the development of plasmodium resistance in malaria endemic areas, due to the exposition to subtherapeutic doses. 5,6 The development of useful and reliable methods for the identification of antimalarials is therefore essential to evaluate the quality of the antimalarial pharmaceutical preparations. Electrospray Ionization Tandem Mass Spectrometry of the Two Main Antimalarial Drugs J. Braz. Chem. Soc. 66 Chromatographic methods for the analysis of artemether and lumefantrine have been reported, focusing on the quantitation of these drugs in pharmaceutical products 7 or biological matrices. 8,9 HPLC with UV detection ...

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“…8 The design of analytical methods for quality control of pharmaceutical products should be an important research objective to ensure public health improvement. Despite the frequent use of fixed-dose combination tablets of ARS and MFQ, no method for their quality control has been described in the pharmacopoeias.…”

Section: Simultaneous Determination Of Antimalarial Agents By Lc-ms/mmentioning

confidence: 99%

“…7 Hence, reliable alternatives for public quality inspection control of antimalarial drugs may help to ensure treatment efficacy and avoid the development of resistance to antimalarial drugs. 8 The design of analytical methods for quality control of pharmaceutical products should be an important research objective to ensure public health improvement. Despite the frequent use of fixed-dose combination tablets of ARS and MFQ, no method for their quality control has been described in the pharmacopoeias.…”

Section: Simultaneous Determination Of Antimalarial Agents By Lc-ms/mmentioning

confidence: 99%

Simultaneous Determination of Antimalarial Agents by LC-MS/MS and Its Application to Evaluation of Fixed-Dose Tablets

Marson¹,

Vilhena²,

Pontes³

et al. 2016

J. Braz. Chem. Soc.

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We developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify the antimalarials artesunate (ARS) and mefloquine (MFQ) in fixed-dose tablets. The detection was performed by a triple-quadrupole mass spectrometer in multiple reaction monitoring (MRM) in positive ion mode via electrospray ionization. Chromatographic separation was achieved with an XBridge C18 column (50 × 2.1 mm, 5 μm), using isocratic elution (350 μL min -1 ) of water/acetonitrile/methanol (30:35:35, v/v/v) containing 0.1% formic acid. The method was validated according to the International Conference of Harmonization (ICH) guidelines. The calibration curves obtained for ARS (400 to 600 ng mL -1 ) and MFQ (800 to 1200 ng mL -1 ) showed good linearity (r 2 > 0.99), precision (relative standard deviation (RSD): ARS < 2.0%; MFQ < 1.9%), and accuracy (recoveries: ARS, 102.4-103.4%; MFQ, 97.4-101.6%), and were stable for 24 h at 8 °C. The method was successfully applied to commercial tablets, and recoveries of 98.7 ± 4.7% (ARS) and 105.6 ± 3.13% (MFQ). The method developed is a reliable alternative for public quality inspection control with the advantage of tandem mass specificity and speed. Keywords: antimalarial, artesunate, LC-MS/MS, mefloquine, validation IntroductionMalaria is an infectious disease caused by protozoan parasites of the genus Plasmodium.1 Several Plasmodium species are known to infect humans, and Plasmodium falciparum is considered the most dangerous species, since it is responsible for the most severe and fatal cases of malaria.2 Malaria is one of the most serious public health concerns worldwide and 3.2 billion people remain at risk of being infected. In 2015, 214 million new cases of malaria and 438,000 deaths were reported. 2 The treatment of malaria is based on targeting the lifecycle of the parasite. The World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs), such as artesunate (ARS) (C 19 (Figure 1), for the treatment of uncomplicated malaria, caused by P. falciparum. 2,3ACTs combine two active drugs with different mechanisms of action in order to increase the spectrum of activity and effectiveness, and to prevent antimalarial drug resistance. In an ACT, the immediate effect of an artemisinin derivative, which rapidly clears asexual blood-stage parasites and gametocytes, is combined with J. Braz. Chem. Soc. 616 a drug of a different class that has a longer half-life, thus eliminating residual parasites. 4,5 One of the barriers in the fight against malaria is the increasing presence on the market of counterfeit drugs, which, in recent years, has led to the development of P. falciparum resistance to therapy. Simultaneous Determination of Antimalarial Agents by LC-MS/MS and Its Application6 Antimalarials are among the most widely administered drugs in tropical countries and have been particularly targeted by counterfeiters. The use of counterfeit drugs or substandard antimalarial drugs can cause increased morbidity, adverse effects, and mortal...

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Simultaneous determination of artemether and lumefantrine in fixed dose combination tablets by HPLC with UV detection

Cited by 43 publications

References 13 publications

Artemether–Lumefantrine Concentrations in Tablets and Powders from Ghana Measured by a New High-Performance Liquid Chromatography Method

Artemether–Lumefantrine Concentrations in Tablets and Powders from Ghana Measured by a New High-Performance Liquid Chromatography Method

Electrospray ionization tandem mass spectrometry of the two main antimalarial drugs: artemether and lumefantrine

Simultaneous Determination of Antimalarial Agents by LC-MS/MS and Its Application to Evaluation of Fixed-Dose Tablets

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