Stability-indicating HPLC-DAD/UV-ESI/MS impurity profiling of the anti-malarial drug lumefantrine
Abstract Background Lumefantrine (benflumetol) is a fluorene derivative belonging to the aryl amino alcohol class of anti-malarial drugs and is commercially available in fixed combination products with β-artemether. Impurity characterization of such drugs, which are widely consumed in tropical count...
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ftdoajarticles:oai:doaj.org/article:d8ce30df70374709926ec9a19b7d1e17 2023-05-15T15:11:19+02:00 Stability-indicating HPLC-DAD/UV-ESI/MS impurity profiling of the anti-malarial drug lumefantrine Duchateau Luc Burvenich Christian Van Dorpe Sylvia Vangheluwe Elien Baert Bram Suleman Sultan Verbeken Mathieu Jansen Frans H De Spiegeleer Bart 2011-02-01T00:00:00Z https://doi.org/10.1186/1475-2875-10-51 https://doaj.org/article/d8ce30df70374709926ec9a19b7d1e17 EN eng BMC http://www.malariajournal.com/content/10/1/51 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-10-51 1475-2875 https://doaj.org/article/d8ce30df70374709926ec9a19b7d1e17 Malaria Journal, Vol 10, Iss 1, p 51 (2011) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2011 ftdoajarticles https://doi.org/10.1186/1475-2875-10-51 2022-12-31T13:44:50Z Abstract Background Lumefantrine (benflumetol) is a fluorene derivative belonging to the aryl amino alcohol class of anti-malarial drugs and is commercially available in fixed combination products with β-artemether. Impurity characterization of such drugs, which are widely consumed in tropical countries for malaria control programmes, is of paramount importance. However, until now, no exhaustive impurity profile of lumefantrine has been established, encompassing process-related and degradation impurities in active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs). Methods Using HPLC-DAD/UV-ESI/ion trap/MS, a comprehensive impurity profile was established based upon analysis of market samples as well as stress, accelerated and long-term stability results. In-silico toxicological predictions for these lumefantrine related impurities were made using Toxtree ® and Derek ® . Results Several new impurities are identified, of which the desbenzylketo derivative (DBK) is proposed as a new specified degradant. DBK and the remaining unspecified lumefantrine related impurities are predicted, using Toxtree ® and Derek ® , to have a toxicity risk comparable to the toxicity risk of the API lumefantrine itself. Conclusions From unstressed, stressed and accelerated stability samples of lumefantrine API and FPPs, nine compounds were detected and characterized to be lumefantrine related impurities. One new lumefantrine related compound, DBK, was identified and characterized as a specified degradation impurity of lumefantrine in real market samples (FPPs). The in-silico toxicological investigation (Toxtree ® and Derek ® ) indicated overall a toxicity risk for lumefantrine related impurities comparable to that of the API lumefantrine itself. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 10 1 51 |
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Directory of Open Access Journals: DOAJ Articles |
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language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Duchateau Luc Burvenich Christian Van Dorpe Sylvia Vangheluwe Elien Baert Bram Suleman Sultan Verbeken Mathieu Jansen Frans H De Spiegeleer Bart Stability-indicating HPLC-DAD/UV-ESI/MS impurity profiling of the anti-malarial drug lumefantrine |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Lumefantrine (benflumetol) is a fluorene derivative belonging to the aryl amino alcohol class of anti-malarial drugs and is commercially available in fixed combination products with β-artemether. Impurity characterization of such drugs, which are widely consumed in tropical countries for malaria control programmes, is of paramount importance. However, until now, no exhaustive impurity profile of lumefantrine has been established, encompassing process-related and degradation impurities in active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs). Methods Using HPLC-DAD/UV-ESI/ion trap/MS, a comprehensive impurity profile was established based upon analysis of market samples as well as stress, accelerated and long-term stability results. In-silico toxicological predictions for these lumefantrine related impurities were made using Toxtree ® and Derek ® . Results Several new impurities are identified, of which the desbenzylketo derivative (DBK) is proposed as a new specified degradant. DBK and the remaining unspecified lumefantrine related impurities are predicted, using Toxtree ® and Derek ® , to have a toxicity risk comparable to the toxicity risk of the API lumefantrine itself. Conclusions From unstressed, stressed and accelerated stability samples of lumefantrine API and FPPs, nine compounds were detected and characterized to be lumefantrine related impurities. One new lumefantrine related compound, DBK, was identified and characterized as a specified degradation impurity of lumefantrine in real market samples (FPPs). The in-silico toxicological investigation (Toxtree ® and Derek ® ) indicated overall a toxicity risk for lumefantrine related impurities comparable to that of the API lumefantrine itself. |
format |
Article in Journal/Newspaper |
author |
Duchateau Luc Burvenich Christian Van Dorpe Sylvia Vangheluwe Elien Baert Bram Suleman Sultan Verbeken Mathieu Jansen Frans H De Spiegeleer Bart |
author_facet |
Duchateau Luc Burvenich Christian Van Dorpe Sylvia Vangheluwe Elien Baert Bram Suleman Sultan Verbeken Mathieu Jansen Frans H De Spiegeleer Bart |
author_sort |
Duchateau Luc |
title |
Stability-indicating HPLC-DAD/UV-ESI/MS impurity profiling of the anti-malarial drug lumefantrine |
title_short |
Stability-indicating HPLC-DAD/UV-ESI/MS impurity profiling of the anti-malarial drug lumefantrine |
title_full |
Stability-indicating HPLC-DAD/UV-ESI/MS impurity profiling of the anti-malarial drug lumefantrine |
title_fullStr |
Stability-indicating HPLC-DAD/UV-ESI/MS impurity profiling of the anti-malarial drug lumefantrine |
title_full_unstemmed |
Stability-indicating HPLC-DAD/UV-ESI/MS impurity profiling of the anti-malarial drug lumefantrine |
title_sort |
stability-indicating hplc-dad/uv-esi/ms impurity profiling of the anti-malarial drug lumefantrine |
publisher |
BMC |
publishDate |
2011 |
url |
https://doi.org/10.1186/1475-2875-10-51 https://doaj.org/article/d8ce30df70374709926ec9a19b7d1e17 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 10, Iss 1, p 51 (2011) |
op_relation |
http://www.malariajournal.com/content/10/1/51 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-10-51 1475-2875 https://doaj.org/article/d8ce30df70374709926ec9a19b7d1e17 |
op_doi |
https://doi.org/10.1186/1475-2875-10-51 |
container_title |
Malaria Journal |
container_volume |
10 |
container_issue |
1 |
container_start_page |
51 |
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1766342193514020864 |