Forced degradation studies and structural characterization of related substances of bisoprolol fumarate in finished drug product using LC–UV–MS/MS Scientific paper

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Elena Lazarevska Todevska
Marjan Piponski
Marina Stefova


Methods for determination of bisoprolol and related substances mostly use UV detection and a phosphate buffer and are not suitable for MS detection. In this study, LC–UV–MS/MS for separation and characterization of bisoprolol related substances was developed, validated and applied for study­ing the degradation products of bisoprolol when exposed to hydrolytic stress, heat and light. The method uses a C18 column, formic acid in water and aceto­nitrile as mobile phases, gradient elution and UV and MS detection. Forced degrad­ation revealed that acid hydrolysis produces the most intensive trans­form­ation of bisoprolol to its impurity A, along with impurities L and D. Alk­aline hyd­rolysis produced impurities A, L, Q, G and K; oxidative and thermal degrad­ation produced impurities A, L and K, while photodegradation produced imp­urities A, L, G and K, all characterized by their mass spectral data. The dev­eloped method using two detection systems was demonstrated as efficient since mass spectra allowed identification of the related substances of bisoprolol and quantification was possible using absorbance measurements at 270 nm. The obtained results will fill in the lack of data on the fragmentation patterns of bis­oprolol and related substances that could be used by researchers and prac­tit­ioners in research and quality control laboratories.


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E. . Lazarevska Todevska, M. Piponski, and M. Stefova, “Forced degradation studies and structural characterization of related substances of bisoprolol fumarate in finished drug product using LC–UV–MS/MS: Scientific paper”, J. Serb. Chem. Soc., vol. 87, no. 10, pp. 1185–1202, Jun. 2022.
Analytical Chemistry


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