Injectable solutions containing epinephrine (EPI) and norepinephrine (NE) are not stable, and their degradation is favored mainly by the oxidation of catechol moiety. As studies of these drugs under forced degradation conditions are scarce, herein, we report the identification of their degradation products (DP) in anesthetic formulations by the development of stability‐indicating HPLC method. Finally, the risk assessment of the major degradation products was evaluated using in silico toxicity approach. HPLC method was developed to obtain a higher selectivity allowing adequate elution for both drugs and their DPs. The optimized conditions were developed using a C18 HPLC column, sodium 1‐octanesulfonate, and methanol (80:20, v/v) as mobile phase, with a flow rate of 1.5 mL/min, UV detection at 199 nm. The analysis of standard solutions with these modifications resulted in greater retention time for EPI and NE, which allow the separation of these drugs from their respective DPs. Then, five DPs were identified and analyzed by in silico studies. Most of the DPs showed important alerts as hepatotoxicity and mutagenicity. To the best of our acknowledgment, this is the first report of a stability‐indicating HPLC method that can be used with formulations containing catecholamines.

中文翻译：

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牙科麻醉药对去甲肾上腺素和肾上腺素的强迫降解研究：稳定性指示HPLC方法的发展和计算机毒性评估。

含有肾上腺素（EPI）和去甲肾上腺素（NE）的可注射溶液不稳定，主要通过儿茶酚部分的氧化促进其降解。由于缺乏在强制降解条件下对这些药物的研究，因此，本文报道了通过开发指示稳定性的HPLC方法鉴定麻醉剂中其降解产物（DP）的方法。最后，使用计算机毒性法评估了主要降解产物的风险评估。开发了HPLC方法以获得更高的选择性，从而可以对药物及其DP进行充分洗脱。使用C18 HPLC色谱柱，1-辛烷磺酸钠和甲醇（80:20，v / v）作为流动相，以1.5 mL / min的流速，在199 nm处进行UV检测确定了最佳条件。对具有这些修饰的标准溶液进行分析，可以延长EPI和NE的保留时间，从而使这些药物与各自的DP分离。然后，通过计算机研究确定了五个DP，并进行了分析。大多数DP表现出重要的警报，如肝毒性和致突变性。据我们所知，这是可用于含儿茶酚胺制剂的稳定性指示HPLC方法的首次报道。