Quality control of active ingredients in artemisinin‐derivative antimalarials within Kenya and DR Congo

• Published in: Tropical medicine & international health 2007-01, Vol.12 (1), p.68-74
• Main Authors: Atemnkeng, Magnus A., De Cock, Katelijne, Plaizier‐Vercammen, Jacqueline
• Format: Article
• Language: English
• Subjects: adulterados; antimalarials; Antimalarials - analysis; Antimalarials - therapeutic use; Antimalariques; Antimaláricos; artemisinin derivatives; Artemisinins - analysis; Artemisinins - therapeutic use; Biological and medical sciences; Capsules; Chromatography, High Pressure Liquid - methods; Consumer protection; contrefaçon; control de calidad; contrôle de qualité; counterfeit; Counterfeiting; Democratic Republic of the Congo - epidemiology; derivados de la artemisinina; Dosage Forms; Drug dosages; dérivés d'artemisinine; Endemic Diseases; General aspects; HPLC en phase inversée; HPLC fase revertida; Humans; Kenya - epidemiology; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - epidemiology; Medical sciences; Plasmodium falciparum; Prescription drugs; Product testing; Public health; Quality Control; reversed‐phase HPLC; Sesquiterpenes - analysis; Sesquiterpenes - therapeutic use; Tablets
• ISSN: 1360-2276; 1365-3156
• DOI: 10.1111/j.1365-3156.2006.01769.x

Summary Objectives  Artemisinin‐derivative drugs are widely used to treat Plasmodium falciparum malaria and very few studies have investigated the quality of these medicines in Africa. We analysed the active ingredient contents of artemisinin‐derivative drugs marketed in Kenya and DR Congo. Methods  We analysed tablets, capsules, dry suspensions and injections (IM) containing either artemether (AM), arteether (AE), artesunate (ARS) or dihydroartemisinin (DHA). The content of active ingredients and preservatives was determined quantitatively using validated HPLC‐UV methods. All analyses were done according to European pharmacopoeia requirements. Results  Labelled active ingredients were identified in all samples, however with varying dosages. Nine of the 24 drug samples analysed did not comply with the pharmacopoeial requirements of 95–105%: seven samples were underdosed and two were slightly overdosed. DHA was the active ingredient in 57% of the underdosed samples. AE injections had the lowest drug content (77%). Two‐thirds of the dry powder suspensions were either substandard or fake. Tablets were up to 23% out of range. Unidentified peaks were observed on the chromatograms of AE IM injections and a DHA dry powder. Conclusions  Counterfeit or substandard artemisinin‐derivative drugs are being sold in parts of Africa, presenting a potential route for resistance development in the future. Appropriate measures need to be taken to maintain proper and safe use of these medicines. Objectifs  Les médicaments dérivés d'artemisinine sont largement utilisés pour le traitement de malaria Plasmodium falciparum mais très peu d’études ont investigué la qualité de ces medicaments en Afrique.Nous avons analysé le contenu en principes actifs de médicaments derivés d'artemisinine vendus au Kenya et en République Démocratique du Congo. Méthodes  Nous avons analysé les comprimés, les gélules, les suspensions sèches et les injetables contenant soit l'artemether, l'arteether, l'artesunate ou la dihydroartemisinine. La teneur en principe actifs et en conservateurs a été determinée quantitativement par des méthodes HPLC‐UV. Toutes les analyses ont été effectuées selon la Pharmacopée Européenne. Résultats  Les principes actifs mentionnés sur les étiquetes ont été identifiés dans tous les echantillons avec cependant des doses variables. Neuf échantillons sur les 24 analysés ne satisfaisaient pas aux exigences 95–105% de la Pharmacopée Européenne. Sept échantillons avaient une dose