Limits...
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

Shows the detection of the artemisinin component from 100% (which is the tablet containing the correct amount of the active principal ingredient as stated on the packet) down to 50% and 10% (which will imply that the product is substandard or counterfeit) in formulations of artesunate/amodiaquine (AS/AQ;100%  =  50 mg, 50%  = 25 mg and 10%  =  5 mg), artemether/lumefantrine (AM/LUM, Coartem®; 100%  =  20 mg, 50%  = 10 mg and 10%  =  2 mg), and dihydroartemisinin/piperaquine (DHA/PIP, Duocortexin®; 100%  =  40 mgs, 50%  = 20 mg and 10%  =  4 mg).
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pone-0007270-g006: Shows the detection of the artemisinin component from 100% (which is the tablet containing the correct amount of the active principal ingredient as stated on the packet) down to 50% and 10% (which will imply that the product is substandard or counterfeit) in formulations of artesunate/amodiaquine (AS/AQ;100%  =  50 mg, 50%  = 25 mg and 10%  =  5 mg), artemether/lumefantrine (AM/LUM, Coartem®; 100%  =  20 mg, 50%  = 10 mg and 10%  =  2 mg), and dihydroartemisinin/piperaquine (DHA/PIP, Duocortexin®; 100%  =  40 mgs, 50%  = 20 mg and 10%  =  4 mg).

Mentions: The limits of detection for the co-formulations (WINTHROP - artesunate/amodiaquine, Coartem®-artemether/lumefantrine and Duocortexcin - dihydroartemisinin/piperaquine) was determined by pulverising each representative tablet and dissolving in methanol (2 mL). Further dilutions were carried out to achieve 50% and 10% solutions and 10 µL of each solution was then applied to the TLC plate followed by either DNP or FBS solutions (10 µL each) and the resulting colour is shown Figure 6. The depth of colour with DNP was achieved within 10 min and with FBS was achieved within 40 min, and for both the depth of colour was stable for up to 2 weeks.


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

Ioset JR, Kaur H - PLoS ONE (2009)

Shows the detection of the artemisinin component from 100% (which is the tablet containing the correct amount of the active principal ingredient as stated on the packet) down to 50% and 10% (which will imply that the product is substandard or counterfeit) in formulations of artesunate/amodiaquine (AS/AQ;100%  =  50 mg, 50%  = 25 mg and 10%  =  5 mg), artemether/lumefantrine (AM/LUM, Coartem®; 100%  =  20 mg, 50%  = 10 mg and 10%  =  2 mg), and dihydroartemisinin/piperaquine (DHA/PIP, Duocortexin®; 100%  =  40 mgs, 50%  = 20 mg and 10%  =  4 mg).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0007270-g006: Shows the detection of the artemisinin component from 100% (which is the tablet containing the correct amount of the active principal ingredient as stated on the packet) down to 50% and 10% (which will imply that the product is substandard or counterfeit) in formulations of artesunate/amodiaquine (AS/AQ;100%  =  50 mg, 50%  = 25 mg and 10%  =  5 mg), artemether/lumefantrine (AM/LUM, Coartem®; 100%  =  20 mg, 50%  = 10 mg and 10%  =  2 mg), and dihydroartemisinin/piperaquine (DHA/PIP, Duocortexin®; 100%  =  40 mgs, 50%  = 20 mg and 10%  =  4 mg).
Mentions: The limits of detection for the co-formulations (WINTHROP - artesunate/amodiaquine, Coartem®-artemether/lumefantrine and Duocortexcin - dihydroartemisinin/piperaquine) was determined by pulverising each representative tablet and dissolving in methanol (2 mL). Further dilutions were carried out to achieve 50% and 10% solutions and 10 µL of each solution was then applied to the TLC plate followed by either DNP or FBS solutions (10 µL each) and the resulting colour is shown Figure 6. The depth of colour with DNP was achieved within 10 min and with FBS was achieved within 40 min, and for both the depth of colour was stable for up to 2 weeks.

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