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All monographs published in The International Pharmacopoeias artemisin derivatives, (i.e. artemether, artemisinin, artemotil, and artenimol as active ingredients and dosage forms) have the same limits for the related substances tests (HPLC and TLC) with the exception of artesunate. Artesunate (active ingredient and tablets) has higher limits than the others due to the fact that this substance was considered to be less stable. However, comments received from different parties and experimental verification by the WHO Collaborating Centre for Drug Quality Assurance, People's Republic of China, suggest that the limits on artesunate should be reconsidered and brought in line with the other International Pharmacopoeia monographs on artemisinin derivatives. In addition, in all monographs on artemisinin derivatives except artesunate, a test for loss of drying is described. For artesunate, a test for water content is described. The proposals below would bring the monographs on artesunate in line with the other artemisinin derivative monographs.
Please address any comments you may have to: Quality Assurance and Safety: Medicines, Medicines Policy and Standards, World Health Organization, 1211 Geneva 27, Switzerland, fax: (+41 22)791 4730 or e-mail: [email protected] and rabouhansm@ who.int.
Atresunate
Related substances
It is proposed to amend the limits as follows:
HPLC
* Any impurity: not more than 0.5% (instead of 1.0%)
* Not more than one impurity above 0.25% (instead of 0.5%)
* Total of impurities: not more than 1.0% (instead of 2.0%)
* Disregard limit: 0.05% (instead of 0.1%)
TLC
* Any impurity spot is not more intense than 0.5% (instead of 1.0%)
* Not more than one impurity spot is more intense than 0.25% (instead of 0.5%)
HPLC assay limits
If it is agreed to revise the related substances tests as proposed above, consideration should be given to revising the HPLC assay limits to 97.0 %-102.0 % (instead of 96.0 %-102.0 %).
Water
It is proposed to replace the test for water by a test on loss of drying.
Drying at 60 °C under reduced pressure (not more than 2.67 kPa) has been suggested. The test could either specify drying to constant mass (as artemisinin) or specify a time, if a suitable time is available.
A suitable limit will need to be agreed (e.g. 0.5 % as for artemether or 1.0 % as for artenimol may...