Abstract：
Tetrodotoxin (TTX) is a potent marine neurotoxin, responsible for numerous poisoning incidents and some human fatalities. To date, more than 30 TTX analogues have been identified, but their individual toxicities and roles in poisoning remain largely unknown. In this work, the toxicity equivalency factors (TEFs) of five TTX analogues were determined by assessing the blockade of voltage-gated sodium channels in Neuro-2a cells using automated patch clamp (APC). All TTX analogues were less toxic than TTX. The derived TEFs were applied to the individual TTX analogues concentrations measured in pufferfish samples, using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A comparison of these results with those obtained from APC analysis demonstrated that TEFs can be effectively used to translate LC-MS/MS analytical data into meaningful toxicological information. This is the first study to utilize APC device for the toxicological assessment of TTX analogues, highlighting its potential as a bioanalytical tool for seafood safety management and human health protection.
摘要：
河豚毒素（TTX）是一种强效的海洋神经毒素，对许多中毒事件和一些人死亡负责。迄今为止,已鉴定出30多种TTX类似物，但是他们的个体毒性和在中毒中的作用在很大程度上仍然未知。在这项工作中,通过使用自动膜片钳(APC)评估Neuro-2a细胞中电压门控钠通道的阻断,确定了5种TTX类似物的毒性等效因子(TEFs).所有TTX类似物的毒性均低于TTX。将衍生的TEF应用于河豚样品中测量的单个TTX类似物浓度，使用液相色谱与串联质谱联用(LC-MS/MS)。这些结果与从APC分析获得的结果的比较表明TEF可以有效地用于将LC-MS/MS分析数据转化为有意义的毒理学信息。这是第一个利用APC装置对TTX类似物进行毒理学评估的研究，强调其作为海产品安全管理和人类健康保护的生物分析工具的潜力。
