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首页> 外文期刊>RSC Advances >Characterization of stress degradation products of mirabegron using UPLC-QTOF-MS/MS and in silico toxicity predictions of its degradation products
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Characterization of stress degradation products of mirabegron using UPLC-QTOF-MS/MS and in silico toxicity predictions of its degradation products

机译：使用UPLC-QTOF-MS / MS表征米拉贝隆的应力降解产物并对其降解产物进行计算机毒性预测

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摘要

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 x 2.1 mm, 1.7 mu m) 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.
机译：Mirabegron是治疗膀胱过度活动症的新型β-3肾上腺素能受体激动剂。根据国际协调会议指南（ICH）Q1A（R2），对药物进行了水解，光解，热和氧化胁迫条件的研究，以了解药物的降解情况。药物中存在的降解产物可能会影响药物的安全性。结果，降解产物的鉴定和表征在药物开发过程中变得非常重要。在这项研究中，使用醋酸铵的梯度洗脱方法，在Waters CSH C-18色谱柱（100 mm x 2.1 mm，1.7μm）上开发了一种简单，快速，精确和准确的超高效液相色谱法（UPLC-PDA）。 （10 mM，pH 5）和乙腈作为流动相。发现Mirabegron在水解和氧化应激条件下会降解，而在热和光解条件下则稳定。通过UPLC-MS / MS在阳离子模式下对总共7种降解产物进行了表征，并进行了精确的质量测量。拟议的降解产物结构已通过适当的机制进行了合理化。此外，通过使用TOPKAT和DEREK软件来提高药物的安全性，可以预测所有降解产物的计算机毒性。

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