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

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Abstract

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.

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Acknowledgements

The authors sincerely thank the No. 4 Pharmaceutical Company Limited (China) for graciously providing samples of terbutaline sulfate. The authors are also thankful for the financial supports from the National Natural Science Foundation of China (81102412), the Ministry of Education Key Project of Science and Technology Foundation of China (211021), Hundreds of Innovative Talents Project of Hebei Education Department of China, and the Natural Science Foundation of Hebei Province of China (C2011206158, 08B031).

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Authors and Affiliations

  1. Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China

    Na Zhou, Qi Qian, Pengcheng Qi, Jie Zhao, Chunying Wang & Qiao Wang

  2. Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China

    Qiao Wang

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  1. Na Zhou
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  2. Qi Qian
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  3. Pengcheng Qi
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  4. Jie Zhao
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Correspondence to Qiao Wang.

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Zhou, N., Qian, Q., Qi, P. et al. Identification of Degradation Products and Process Impurities from Terbutaline Sulfate by UHPLC-Q-TOF-MS/MS and In Silico Toxicity Prediction. Chromatographia 80, 793–804 (2017). https://doi.org/10.1007/s10337-017-3259-5

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  • DOI: https://doi.org/10.1007/s10337-017-3259-5

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