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Simultaneous Determination of Artesunate and Amodiaquine in Fixed-Dose Combination by a RP-HPLC Method with Double UV Detection: Implementation in Interlaboratory Study Involving Seven African National Quality Control Laboratories

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Abstract

The fixed-dose combination artesunate (AS)–amodiaquine (AQ) is one of the most widely used treatments for uncomplicated falciparum malaria. It is currently proposed to the inclusion in the model list of essential medicines of World Health Organization and has been recently prequalified. Until now, no satisfactory method for the simultaneous determination of the two active ingredients had been available. Thus, a reversed phase high performance liquid chromatography for the quantitative determination of AQ and AS was developed and validated. Chromatography was performed using an end-capped octadecylsilyl silica gel column (100 × 4.6 mm, 3 μm) with a binary gradient using aqueous phase containing potassium dihydrogen phosphate (10 mM) and acetonitrile. Taking into consideration the physico-chemical characteristics of the two compounds related to their ionization, the use of a counter ion was necessary to ensure the retention of AQ in a reversed phase system simultaneously to AS. Thus, aqueous mobile phase was adjusted to pH 3.0 and the chosen counter ion was sodium 1-octanesulfonate (100 mM). In these conditions, the retention times were about 4 min for AQ and 10 min for AS with UV detection at 300 and 210 nm, respectively. Method was then validated according to ICH guideline (specificity/linearity/accuracy/precision) and potential interferences with excipients and degradation products were checked. It has also been used for an interlaboratory study involving seven African National Quality Control Laboratories and Afssaps (Agence française de sécurité sanitaire des produits de santé) laboratory. The results demonstrate that this rapid and simple method can be easily used by official laboratories for routine control, market survey and for the detection of potential substandard medicines which are very frequent in African countries.

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Acknowledgments

The authors are very grateful to B. Poirier and H. Thevenin from the Statistical and Methodological Unit from Afssaps Directorate of Laboratories for their helpful contribution in the statistical analysis of the data presented in this paper. The authors express their thanks to S. Renaudin from the French Ministry of Foreign and European Affairs for having ease the logistics of samples and reagents delivery to the African National Quality Control Laboratories and R. Deniau from the International Affairs Department from Afssaps for her help in the animation of the African control laboratories network. This study would have been impossible without the support of Jitka Sabartova from WHO for providing Coarsucam™ tablets and reference substances.

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Authors and Affiliations

  1. Direction des laboratoires et des contrôles, Agence française de sécurité sanitaire des produits de santé, 634 rue de la Garenne, 34740, Vendargues Cedex, France

    Y. Le Vaillant, C. Brenier, Y. Grange, P. A. Bonnet & D. Chauvey

  2. Direction des laboratoires et des contrôles, Agence française de sécurité sanitaire des produits de santé, Boulevard Anatole France, 143-147, 93285, Saint-Denis, France

    A. Nicolas

  3. Laboratoire national de contrôle de qualité des médicaments et d’expertise, BP-12216, Yaoundé, Cameroon

    L. R. Massing-Bias

  4. Agence du médicament de Madagascar-BP, BP-8145, 101, Antanarivo, Madagascar

    P. Rakotomanga

  5. Laboratoire national de santé, BPE-4559, Bamako, Mali

    B. Koumaré

  6. Laboratoire national de contrôle de qualité des médicaments, BP-6206, Rabat, Morocco

    A. Mahly

  7. Laboratoire national de santé publique et d’expertise, BP-10465, Niamey, Niger

    M. Absi

  8. Laboratoire national de contrôle de qualité des médicaments, BP-6303, Dakar, Senegal

    M. Ciss

  9. Laboratoire national de contrôle de qualité des médicaments, Bab Saadoun, 1006, Tunis, Tunisia

    M. H. Loueslati

  10. Direction des Laboratoires et des Contrôles, Agence Française de Sécurité Sanitaire des Produits de Santé, CS 60007, 34748, Vendargues Cedex, France

    Y. Le Vaillant

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  1. Y. Le Vaillant
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  2. C. Brenier
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  3. Y. Grange
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  5. P. A. Bonnet
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  6. L. R. Massing-Bias
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  10. M. Absi
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  12. M. H. Loueslati
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  13. D. Chauvey
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Correspondence to Y. Le Vaillant.

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Le Vaillant, Y., Brenier, C., Grange, Y. et al. Simultaneous Determination of Artesunate and Amodiaquine in Fixed-Dose Combination by a RP-HPLC Method with Double UV Detection: Implementation in Interlaboratory Study Involving Seven African National Quality Control Laboratories. Chromatographia 75, 617–628 (2012). https://doi.org/10.1007/s10337-012-2241-5

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  • DOI: https://doi.org/10.1007/s10337-012-2241-5

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