Methyl isocyanate (MIC) is an important precursor for industrial synthesis, but it is highly toxic. MIC causes irritation and damage to the eyes, respiratory tract, and skin. While current treatment is limited to supportive care and counteracting symptoms, promising countermeasures are being evaluated. Our work focuses on understanding the inhalation toxicity of MIC to develop effective therapeutic interventions. However, in-vivo inhalation exposure studies are limited by challenges in estimating the actual respiratory dose, due to animal-to-animal variability in breathing rate, depth, etc. Therefore, a method was developed to estimate the inhaled MIC dose based on analysis of an N-terminal valine hemoglobin adduct. The method features a simple sample preparation scheme, including rapid isolation of hemoglobin, hydrolysis of the hemoglobin adduct with immediate conversion to methyl isopropyl hydantoin (MIH), rapid liquid-liquid extraction, and gas-chromatography mass-spectrometry analysis. The method produced a limit of detection of 0.05 mg MIH/kg RBC precipitate with a dynamic range from 0.05–25 mg MIH/kg. The precision, as measured by percent relative standard deviation, was <8.5%, and the accuracy was within 8% of the nominal concentration. The method was used to evaluate a potential correlation between MIH and MIC internal dose and proved promising. If successful, this method may be used to quantify the true internal dose of MIC from inhalation studies to help determine the effectiveness of MIC therapeutics.

异氰酸甲酯（MIC）是工业合成的重要前体，但剧毒。MIC会刺激眼睛并损害眼睛，呼吸道和皮肤。虽然目前的治疗仅限于支持治疗和抵消症状，但正在评估有前途的对策。我们的工作重点是了解MIC的吸入毒性，以开发有效的治疗干预措施。但是，由于呼吸频率，深度等动物之间的差异，体内吸入暴露研究受到估计实际呼吸剂量的挑战的限制。因此，开发了一种基于分析来估计吸入MIC剂量的方法N末端缬氨酸血红蛋白加合物的合成。该方法具有简单的样品制备方案，包括快速分离血红蛋白，水解血红蛋白加合物，立即转化为甲基异丙基乙内酰脲（MIH），快速液-液萃取和气相色谱质谱分析。该方法的检出限为0.05 mg MIH / kg RBC沉淀物，动态范围为0.05–25 mg MIH / kg。用相对标准偏差百分比测量的精度<8.5％，精度在标称浓度的8％之内。该方法用于评估MIH和MIC内部剂量之间的潜在相关性，并被证明是有希望的。如果成功，此方法可用于量化吸入研究中MIC的真实内部剂量，以帮助确定MIC治疗剂的有效性。和气相色谱质谱分析。该方法的检出限为0.05 mg MIH / kg RBC沉淀物，动态范围为0.05–25 mg MIH / kg。用相对标准偏差百分比测量的精度<8.5％，精度在标称浓度的8％之内。该方法用于评估MIH和MIC内部剂量之间的潜在相关性，并被证明是有希望的。如果成功，此方法可用于量化吸入研究中MIC的真实内部剂量，以帮助确定MIC治疗剂的有效性。和气相色谱质谱分析。该方法的检出限为0.05 mg MIH / kg RBC沉淀物，动态范围为0.05–25 mg MIH / kg。用相对标准偏差百分比测量的精度<8.5％，精度在标称浓度的8％之内。该方法用于评估MIH和MIC内部剂量之间的潜在相关性，并被证明是有希望的。如果成功，此方法可用于量化吸入研究中MIC的真实内部剂量，以帮助确定MIC治疗剂的有效性。该方法用于评估MIH和MIC内部剂量之间的潜在相关性，并被证明是有希望的。如果成功，此方法可用于量化吸入研究中MIC的真实内部剂量，以帮助确定MIC治疗剂的有效性。该方法用于评估MIH和MIC内部剂量之间的潜在相关性，并被证明是有希望的。如果成功，此方法可用于量化吸入研究中MIC的真实内部剂量，以帮助确定MIC治疗剂的有效性。