Identification of Degradation Products and Process Impurities from Terbutaline Sulfate by UHPLC-Q-TOF-MS/MS and In Silico Toxicity Prediction

A rapid ultrahigh-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) method has been developed for the identification of degradation products and process impurities of terbutaline sulfate. Terbutaline sulfate was subjected to long-term storage and stress degradation conditions of hydrolysis (acidic, neutral and alkaline), oxidation, heat, humidity and photolysis. The separation was achieved on a phenomenex luna C18 (150 mm × 2.0 mm, 3 μm) column using a mobile phase composed of ammonium formate buffer (10 mM, pH 3.2) and methanol in gradient elution mode. A total of 17 compounds including 14 novel degradation products were characterized. Terbutaline sulfate was found to be highly susceptible to oxidative, alkaline hydrolytic and alkaline photolytic conditions. The most probable mechanisms for the formation of degradation products have been proposed for the first time. The in silico toxicity of the drug and its degradation products was assessed using toxicity prediction by computer-assisted technology (TOPKAT) software.