Document Detail


On the formation of bromhexine impurity E and its chromatographic behaviour.
MedLine Citation:
PMID:  23327897     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
B J Venhuis; M Weda; D de Kaste; E K Lamme
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pharmeuropa bio & scientific notes     Volume:  2012     ISSN:  2075-2164     ISO Abbreviation:  Pharmeur Bio Sci Notes     Publication Date:  2012  
Date Detail:
Created Date:  2013-01-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101510163     Medline TA:  Pharmeur Bio Sci Notes     Country:  France    
Other Details:
Languages:  eng     Pagination:  135-41     Citation Subset:  IM    
Affiliation:
National Institute for Public Health and the Environment, Bilthoven, Netherlands.
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