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

Abstract

Methods for determination of bisoprolol and related substances mostly use UV detection and 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 C18 column, formic acid in water and acetonitrile as mobile phases, gradient elution, 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, and 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 measurement at 270 nm. The obtained results will fill in the lack of data on the fragmentation patterns of bisoprolol and related substances that can be used by researchers and practitioners in research and quality control laboratories.

LC–MS/MS bioanalytical method for the quantitative analysis of nifedipine, bisoprolol, and captopril in human plasma: Application to pharmacokinetic studies

“…From the literature survey, various approaches have been reported for the estimation of NIF, CAP and BIS alone or in combination with other drugs. The reported methods include HPLC (Ahmed et al, 2018; Andal et al, 2022; Bahgat et al, 2022; Kondratova et al, 2017; Rashid et al, 2022; Rastkari et al, 2013; Sultan et al, 2013; Sultana et al, 2011; Tatar Ulu & Aydoğmuş, 2012), LC–MS/MS (Giebułtowicz et al, 2015; Grigoriev et al, 2016; Logoyda, 2020; Logoyda et al, 2020; Logoyda et al, 2021; Todevska et al, 2022; Tonooka‐Kubota et al, 2022; Tutunji et al, 2009; Zhao et al, 2023), HPTLC (Aayushi & Shah, 2022; Chitlange et al, 2009; Kakde et al, 2008; Shah et al, 2019), spectrofluorimetric (Abd Elhaleem et al, 2022; Abdelwahab et al, 2018; Attia et al, 2023; Derayea et al, 2022; Dewangan et al, 2022; Dong et al, 2022; Han et al, 2022; Khan et al, 2014; Roshdy et al, 2023; Sheng et al, 2022; Wang et al, 2022; Wu et al, 2022; Xi et al, 2022), UV spectrophotometric (Abed, 2020; Gouda & Amin, 2010; Gudruman et al, 2012; Hamad et al, 2023; Mishra, 2022; Tulasamma & Venkateswarlu, 2016; Ulu & Kel, 2012) and electrochemical methods (Al‐Farhan et al, 2023; Frag et al, 2019; Górska et al, 2022; Hassan et al, 2022; Karimi‐Maleh et al, 2017; Khairy et al, 2017; Koçak & İpek, 2022; Mokhtari et al, 2018; Mourad et al, 2020; Pourhakkak et al, 2022; Soomro et al, 2017; Zare et al, …”