Post-marketing assessment of content and efficacy of preservatives in artemisinin-derived antimalarial dry suspensions for paediatric use

Atemnkeng, Magnus A.; Cock, Katelijne De; Plaizier-Vercammen, Jacqueline

doi:10.1186/1475-2875-6-12

Cited by 16 publications

(13 citation statements)

References 8 publications

(8 reference statements)

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“…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.…”

mentioning

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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mentioning

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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“…This is an advantage over crushed tablets, where loss of some of the pill can lead to suboptimal dosing, and also over dry powder and syrup formulations, where accurate dosing requires precise volume measuring in the field (3). In addition, stability cannot be guaranteed when syrups and powders are reconstituted, particularly in hot climates (5). AL Dispersible tablets are provided in dose blister packs that offer protection from contamination and also from humidity and damage (30).…”

Section: Discussionmentioning

confidence: 99%

“…Dry powders intended for suspension in water have been developed for pediatric use but are often substandard relative to tablets, may contain ineffective or incorrect amounts of preservatives, and are also prone to contamination when reconstituted (5,6). While liquid formulations such as syrups may be among the pediatric formulations preferred by some health professionals, their stability is often limited, particularly in hot climates.…”

mentioning

confidence: 99%

Tailoring a Pediatric Formulation of Artemether-Lumefantrine for Treatment of Plasmodium falciparum Malaria

Bassat

Ogutu

Djimdé

et al. 2015

Antimicrob Agents Chemother

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Specially created pediatric formulations have the potential to improve the acceptability, effectiveness, and accuracy of dosing of artemisinin-based combination therapy (ACT) in young children, a patient group that is inherently vulnerable to malaria. Artemether-lumefantrine (AL) Dispersible is a pediatric formulation of AL that is specifically tailored for the treatment of children with uncomplicated Plasmodium falciparum malaria, offering benefits relating to efficacy, convenience and acceptance, accuracy of dosing, safety, sterility, stability, and a pharmacokinetic profile and bioequivalence similar to those of crushed and intact AL tablets. However, despite being the first pediatric antimalarial to meet World Health Organization (WHO) specifications for use in infants and children who are >5 kg in body weight and its inclusion in WHO Guidelines, there are few publications that focus on AL Dispersible. Based on a systematic review of the recent literature, this paper provides a comprehensive overview of the clinical experience with AL Dispersible to date. A randomized, phase 3 study that compared the efficacy and safety of AL Dispersible to those of crushed AL tablets in 899 African children reported high PCR-corrected cure rates at day 28 (97.8% and 98.5% for AL Dispersible and crushed tablets, respectively), and the results of several subanalyses of these data indicate that this activity is observed regardless of patient weight, food intake, and maximum plasma concentrations of artemether or its active metabolite, dihydroartemisinin. These and other clinical data support the continued use of pediatric antimalarial formulations in all children <5 years of age with uncomplicated malaria when accompanied by continued monitoring for the emergence of resistance.

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“…The equilibrium distribution of various iodine forms (free iodine, triiodide, polymeric iodine triiodide and triiodide complexes, and iodide ion) in aqueous solutions of povidone-iodine drugs has been analyzed. 65 The choice of HMWC allows the concentration of free iodine to be maintained at a level of bactericidal effect (5 mg L -1 ). The presence of polyiodide chains in the structures de pends, to some degree, on the HMWC structure.…”

Section: Organic Iodine Halidesmentioning

confidence: 99%

Organoiodine complexes: Structural and functional variety

Chernov’yants

Бурыкин

2009

Russ Chem Bull

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The present review summarizes the results of structural studies of organoiodine complexes. Particular emphasis is given to the role of intermolecular interactions such as halogenhalogen (I...I), hydrophobic, π-π stacking, and hydrogen bonds (C-H...I) in the formation of supramolecular iodine containing architectures. The molecular formula, size, shape, and stability of the polyhalide ion and the way of its coordination by an outer sphere cation or an organic macromolecule depend on the nature and symmetry of the cationic environment, the ability of a solvating solvent to form complexes with iodine, and the conditions of the synthesis. Efforts have been made to highlight a structural and functional variety of iodine containing complexes and estimate the prospects of using them as organic conductors, magnetic materials, liquid electrolytes, and biologically active compounds.

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Post-marketing assessment of content and efficacy of preservatives in artemisinin-derived antimalarial dry suspensions for paediatric use

Cited by 16 publications

References 8 publications

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

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

Tailoring a Pediatric Formulation of Artemether-Lumefantrine for Treatment of Plasmodium falciparum Malaria

Organoiodine complexes: Structural and functional variety

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