Characterization of stress degradation products of mirabegron using UPLC-QTOF-MS/MS and in silico toxicity predictions of its degradation products

• Published in: RSC advances 2015-01, Vol.5 (39), p.3124-3138
• Main Authors: Kalariya, Pradipbhai D, Sharma, Mahesh, Garg, Prabha, Thota, Jagadeshwar Reddy, Ragampeta, Srinivas, Talluri, M. V. N. Kumar
• Format: Article
• Language: English
• Subjects: Acetonitrile; Computer programs; Conferences; Degradation; Drugs; Guidelines; Product safety; Stresses
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c5ra01711d

Mirabegron is a novel beta-3 adrenergic receptor agonist in the treatment of overactive bladder disorder. The drug was subjected to hydrolytic, photolytic, thermal and oxidative stress conditions as per the International Conference on Harmonization guidelines (ICH) Q1A (R2) to understand the degradation profile of the drug. The safety of the drug may be affected by degradation products present in the drug. As a result, identification and characterization of degradation products has become very important in drug development processes. In this study, a simple, rapid, precise and accurate ultra performance liquid chromatography (UPLC-PDA) method has been developed on a Waters CSH C 18 column (100 mm × 2.1 mm, 1.7 μm) using gradient elution of ammonium acetate (10 mM, pH 5) and acetonitrile as mobile phase. Mirabegron was found to degrade under hydrolytic and oxidative stress conditions while it was stable under thermal and photolytic conditions. A total of seven degradation products were characterized by UPLC-MS/MS in positive ion mode, combined with accurate mass measurements. The proposed structures of the degradation products have been rationalized by appropriate mechanisms. Additionally, in silico toxicity was predicted for all degradant products by using TOPKAT and DEREK softwares to enhance the safety of the drug. Mirabegron is a novel beta-3 adrenergic receptor agonist in the treatment of overactive bladder disorder.