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Simple field assays to check quality of current artemisinin-based antimalarial combination formulations.

Ioset JR, Kaur H - PLoS ONE (2009)

Bottom Line: Artemisinin derivatives (ARTs; artesunate, artemether, and dihydroartemisinin) derived from the herb, Artemisia annua, are the most effective antimalarial drugs available providing rapid cures.Reports of ad hoc surveys from South East Asia show that up to 50% of the artesunate currently sold is counterfeit.We are able to detect as low as 10% of ARTs in ACTs (WINTHROP--artesunate/amodiaquine, Coartem--artemether/lumefantrine and Duocortexcin--dihydroartemisinin/piperaquine).

View Article: PubMed Central - PubMed

Affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.

ABSTRACT

Introduction: Malaria continues to be one of the major public health problems in Africa, Asia and Latin America. Artemisinin derivatives (ARTs; artesunate, artemether, and dihydroartemisinin) derived from the herb, Artemisia annua, are the most effective antimalarial drugs available providing rapid cures. The World Health Organisation (WHO) has recommended that all antimalarials must be combined with an artemisinin component (artemisinin-based combination therapy; ACT) for use as first line treatment against malaria. This class of drugs is now first-line policy in most malaria-endemic countries. Reports of ad hoc surveys from South East Asia show that up to 50% of the artesunate currently sold is counterfeit. Drug quality is rarely assessed in resource poor countries in part due to lack of dedicated laboratory facilities which are expensive to build, equip and maintain. With a view to address this unmet need we developed two novel colour reaction assays that can be used in the field to check the quality of ARTs.

Methods and findings: Our assays utilise thin layer chromatography silica gel sheets and 2, 4 dinitrophenylhydrazine or 4-Benzoylamino-2, 5-dimethoxybenzenediazonium chloride hemi (zinc chloride) salt as the reagents showing a pink or blue product respectively only in the presence ARTs. We are able to detect as low as 10% of ARTs in ACTs (WINTHROP--artesunate/amodiaquine, Coartem--artemether/lumefantrine and Duocortexcin--dihydroartemisinin/piperaquine). The assays have been validated extensively by testing eighty readily accessible and widely used drugs in malaria endemic countries. None of the other antimalarial drugs or a range of commonly used excipients, antiretroviral drugs or other frequently used drugs from the WHO essential drugs list such as analgesics or antibiotics are detected with our assays.

Conclusions: Our two independent assays requiring no specialist training are specific, simple to use, rapid, robust, reproducible, inexpensive and, have successfully resulted in detecting two counterfeit drugs within a small scale screening survey of over 100 declared artemisinin-containing drugs collected from various Asian and African countries. These promising results indicate that the assays will provide a useful first test to assure the quality of the ACTs formulations in resource poor malaria endemic areas when there is an absence of dedicated medicines quality laboratory facilities.

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Related in: MedlinePlus

TLC chromatogram of the ARTs; showing the different rates of travel by artesunate (AS) reference standard and sample tablet from MiniLab®, dihydroartemisinin (DHA) and artemether (AM) reference standard and sample tablet from MiniLab® (Coartem) on silica gel sheets using chloroform: methanol: acetic acid 98:2:0.1 as an elution system.
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pone-0007270-g002: TLC chromatogram of the ARTs; showing the different rates of travel by artesunate (AS) reference standard and sample tablet from MiniLab®, dihydroartemisinin (DHA) and artemether (AM) reference standard and sample tablet from MiniLab® (Coartem) on silica gel sheets using chloroform: methanol: acetic acid 98:2:0.1 as an elution system.

Mentions: A small spot of solution containing the compound was applied to the TLC sheet, about one centimetre from the base. The sheet was placed in the tank such that the solvent mixture (chloroform: methanol: acetic acid [v/v: 98∶2∶0.1]) was below the level of the spotted solution and then travels up the sheet. The sheet was taken out of the solvent before it reaches the top of the sheet, allowed to dry at room temperature and, sprayed with either the DNP or FBS reagent to detect the ARTs that migrated at different rates on the sheet as shown on Figure 2. The HPLC separation of these ARTs is shown in Figure 3 demonstrating that the techniques are complementary.


Simple field assays to check quality of current artemisinin-based antimalarial combination formulations.

Ioset JR, Kaur H - PLoS ONE (2009)

TLC chromatogram of the ARTs; showing the different rates of travel by artesunate (AS) reference standard and sample tablet from MiniLab®, dihydroartemisinin (DHA) and artemether (AM) reference standard and sample tablet from MiniLab® (Coartem) on silica gel sheets using chloroform: methanol: acetic acid 98:2:0.1 as an elution system.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2749338&req=5

pone-0007270-g002: TLC chromatogram of the ARTs; showing the different rates of travel by artesunate (AS) reference standard and sample tablet from MiniLab®, dihydroartemisinin (DHA) and artemether (AM) reference standard and sample tablet from MiniLab® (Coartem) on silica gel sheets using chloroform: methanol: acetic acid 98:2:0.1 as an elution system.
Mentions: A small spot of solution containing the compound was applied to the TLC sheet, about one centimetre from the base. The sheet was placed in the tank such that the solvent mixture (chloroform: methanol: acetic acid [v/v: 98∶2∶0.1]) was below the level of the spotted solution and then travels up the sheet. The sheet was taken out of the solvent before it reaches the top of the sheet, allowed to dry at room temperature and, sprayed with either the DNP or FBS reagent to detect the ARTs that migrated at different rates on the sheet as shown on Figure 2. The HPLC separation of these ARTs is shown in Figure 3 demonstrating that the techniques are complementary.

Bottom Line: Artemisinin derivatives (ARTs; artesunate, artemether, and dihydroartemisinin) derived from the herb, Artemisia annua, are the most effective antimalarial drugs available providing rapid cures.Reports of ad hoc surveys from South East Asia show that up to 50% of the artesunate currently sold is counterfeit.We are able to detect as low as 10% of ARTs in ACTs (WINTHROP--artesunate/amodiaquine, Coartem--artemether/lumefantrine and Duocortexcin--dihydroartemisinin/piperaquine).

View Article: PubMed Central - PubMed

Affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.

ABSTRACT

Introduction: Malaria continues to be one of the major public health problems in Africa, Asia and Latin America. Artemisinin derivatives (ARTs; artesunate, artemether, and dihydroartemisinin) derived from the herb, Artemisia annua, are the most effective antimalarial drugs available providing rapid cures. The World Health Organisation (WHO) has recommended that all antimalarials must be combined with an artemisinin component (artemisinin-based combination therapy; ACT) for use as first line treatment against malaria. This class of drugs is now first-line policy in most malaria-endemic countries. Reports of ad hoc surveys from South East Asia show that up to 50% of the artesunate currently sold is counterfeit. Drug quality is rarely assessed in resource poor countries in part due to lack of dedicated laboratory facilities which are expensive to build, equip and maintain. With a view to address this unmet need we developed two novel colour reaction assays that can be used in the field to check the quality of ARTs.

Methods and findings: Our assays utilise thin layer chromatography silica gel sheets and 2, 4 dinitrophenylhydrazine or 4-Benzoylamino-2, 5-dimethoxybenzenediazonium chloride hemi (zinc chloride) salt as the reagents showing a pink or blue product respectively only in the presence ARTs. We are able to detect as low as 10% of ARTs in ACTs (WINTHROP--artesunate/amodiaquine, Coartem--artemether/lumefantrine and Duocortexcin--dihydroartemisinin/piperaquine). The assays have been validated extensively by testing eighty readily accessible and widely used drugs in malaria endemic countries. None of the other antimalarial drugs or a range of commonly used excipients, antiretroviral drugs or other frequently used drugs from the WHO essential drugs list such as analgesics or antibiotics are detected with our assays.

Conclusions: Our two independent assays requiring no specialist training are specific, simple to use, rapid, robust, reproducible, inexpensive and, have successfully resulted in detecting two counterfeit drugs within a small scale screening survey of over 100 declared artemisinin-containing drugs collected from various Asian and African countries. These promising results indicate that the assays will provide a useful first test to assure the quality of the ACTs formulations in resource poor malaria endemic areas when there is an absence of dedicated medicines quality laboratory facilities.

Show MeSH
Related in: MedlinePlus