| On the formation of bromhexine impurity E and its chromatographic behaviour. | |
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MedLine Citation:
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PMID: 23327897 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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An unknown bromhexine hydrochloride (BRH) degradation product in BRH oral solutions (finished products) was potentially related to the purity of this API. Several degradation experiments were conducted and its identity and formation were investigated using LC-DAD and LC-DAD-MS/MS. Using the LC method described in the Ph.Eur monograph BRH the degradation product was observed at RRTBRH 0.1 and the specified impurities A-D were ruled out as candidates. Impurity E was initially not considered as a candidate as EDQM reported an expected RRTBRH of 1.8. Still, the LC-DAD-MS/MS results were consistent with the M+ ion for impurity E and its expected fragment ions. Therefore, standard addition was carried out using the Ph. Eur. method which confirmed that the degradation product at RRT 0.1 was impurity E. Upon changing the column type to a column described in the knowledge database, impurity E eluted at an RRT of 1.5. Nevertheless, both columns met all of the criteria in the monograph. The formation of impurity E was even observed in BRH solutions without added reagents. As the conversion from BRH to impurity E requires a source of carbon, we suggest that one BRH molecule degrades through a radical mechanism to a reactive species which subsequently is quenched by another BRH molecule producing impurity E. We suggest the transparency list for BRH to be more explicit on the formation of impurity E, its RRT and the permissible LC columns. |
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Authors:
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B J Venhuis; M Weda; D de Kaste; E K Lamme |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Pharmeuropa bio & scientific notes Volume: 2012 ISSN: 2075-2164 ISO Abbreviation: Pharmeur Bio Sci Notes Publication Date: 2012 |
Date Detail:
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Created Date: 2013-01-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101510163 Medline TA: Pharmeur Bio Sci Notes Country: France |
Other Details:
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Languages: eng Pagination: 135-41 Citation Subset: IM |
Affiliation:
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National Institute for Public Health and the Environment, Bilthoven, Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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