Cyanide, hydrogen sulfide, and methanethiol are common toxic inhalation agents that inhibit mitochondrial cytochrome c oxidase and result in cellular hypoxia, cytotoxic anoxia, apnea, respiratory failure, cardiovascular collapse, seizure and potentially death. While all are occupational gas exposure hazards that have the potential to cause mass casualties from industrial accidents or acts of terrorism, only cyanide has approved antidotes, and each of these has major limitations, including difficult administration in mass-casualty settings. While bisaminotetrazole cobinamide (Cbi(AT)₂) has recently gained attention because of its efficacy in treating these metabolic poisons, there is no method available for the analysis of Cbi(AT)₂ in any biological matrix. Hence, in this study, a simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the analysis of Cbi(AT)₂ in swine plasma. The method is extremely simple, consisting of protein precipitation, separation and drying of the supernatant, reconstitution in an aqueous solvent, and LC-MS/MS analysis. The method produced an LOD of 0.3 μM with a wide dynamic range (2 – 500 μM). Inter- and intraassay accuracies (100 ± 12 % and 100 ± 19 %, respectively) were acceptable and the precision (<12 % and < 9 % relative standard deviation, respectively) was good. The developed method was used to analyze Cbi(AT)₂ from treated swine and the preliminary pharmacokinetic parameters showed impressive antidotal behavior, most notably a long estimated elimination half-life (t_1/2 = 37.5 h). This simple and rapid method can be used to facilitate the development of Cbi(AT)₂ as a therapeutic against toxic cyanide, hydrogen sulfide and methanethiol exposure.

氰化物、硫化氢和甲硫醇是常见的有毒吸入剂，可抑制线粒体细胞色素c氧化酶并导致细胞缺氧、细胞毒性缺氧、呼吸暂停、呼吸衰竭、心血管衰竭、癫痫发作并可能导致死亡。虽然所有这些都是职业性气体接触危害，有可能因工业事故或恐怖主义行为造成大规模伤亡，但只有氰化物获得了批准的解毒剂，而且每一种解毒剂都有很大的局限性，包括在大规模伤亡环境中难以管理。虽然双氨基四唑钴酰胺 (Cbi(AT) ₂ ) 最近因其治疗这些代谢毒物的功效而受到关注，但尚无可用于分析 Cbi(AT) _2的方法在任何生物基质中。因此，在本研究中，开发并验证了一种简单快速的液相色谱-串联质谱 (LC-MS/MS) 方法，用于分析猪血浆中的Cbi(AT) _{2 。}该方法非常简单，包括蛋白质沉淀、分离和干燥上清液、在水性溶剂中重构以及 LC-MS/MS 分析。该方法产生的 LOD 为 0.3 μM，具有宽动态范围 (2 – 500 μM)。批间和批内准确度（分别为 100 ± 12 % 和 100 ± 19 %）是可以接受的，精密度（分别为 < 12 % 和 < 9 % 相对标准偏差）良好。开发的方法用于分析 Cbi(AT) ₂来自经过处理的猪和初步药代动力学参数显示出令人印象深刻的解毒行为，最显着的是估计的长消除半衰期 (t _1/2  = 37.5 h)。这种简单快速的方法可用于促进 Cbi(AT) ₂的开发，作为对抗有毒氰化物、硫化氢和甲硫醇暴露的治疗剂。