Identification and Structural Characterization of Unidentified Impurity in Bisoprolol Film-Coated Tablets

The aim of this study is the identification, structural characterization, and qualification of a degradation impurity of bisoprolol
labeled as Impurity RRT 0.95. This degradation product is considered as a principal thermal degradation impurity identified in
bisoprolol film-coated tablets. The impurity has been observed in the stress thermal degradation study of the drug product. Using
HPLC/DAD/ESI-MS method, a tentative structure was assigned and afterwards confirmed by detailed structural characterization
using NMR spectroscopy. The structure of the target Impurity RRT 0.95 was elucidated as phosphomonoester of bisoprolol, having
relative molecular mass of 406 (positive ionization mode). The structural characterization was followed by qualification of Impurity
RRT 0.95 using several different in silico methodologies. From the results obtained, it can be concluded that no new structural alerts
have been generated for Impurity RRT 0.95 relative to the parent compound bisoprolol. The current study presents an in-depth
analysis of the full characterization and qualification of an unidentified impurity in a drug product with the purpose of properly
defining the quality specification of the product.