The noxious effects from exposure to toxic inhalation hazards (TIHs, such as isocyanates, chlorine, etc.) are known to be triggered by the activation of transient receptor potential ankyrin 1 (TRPA1) ion channel. Antagonists of TRPA1 have shown near complete attenuation of the noxious effects from TIH exposure. One of the TRPA1 antagonists, (1E,3E)-1-(4-fluorophenyl)-2-methyl-1-pentene-3-one oxime (A-967079), has shown impressive efficacy, high selectivity, high potency, and oral bioavailability. Although a validated method to quantify A-967079 in biological matrices is vital for the further development of A-967079 as a therapeutic agent, no method for its analysis from any matrix is currently available. Hence, a rapid and simple HPLC-MS/MS method was developed and validated to quantify A-967079 in rabbit plasma. The method presented here features an excellent LOD of 25 nM and a wide linear range (0.05–200 μM), with good accuracy and precision (100 ± 10.5% and <14.2% relative standard deviation, respectively). The stability of A-967079 in plasma was excellent for most of the storage conditions evaluated. The method was successfully applied to determine A-967079 from treated animals and it may facilitate the development of this TRPA1 antagonist as a therapeutic agent against the noxious effects of TIH exposure.

众所周知，接触有毒吸入危害（TIH，如异氰酸盐、氯等）所产生的有害影响是由瞬时受体电位锚蛋白 1 (TRPA1) 离子通道的激活引发的。TRPA1 拮抗剂已显示出几乎完全减弱 TIH 暴露造成的有害影响。TRPA1 拮抗剂之一 (1 E ,3 E )-1-(4-氟苯基)-2-甲基-1-戊烯-3-酮肟 (A-967079) 已显示出令人印象深刻的功效、高选择性、高效力和口服生物利用度。尽管量化生物基质中 A-967079 的经过验证的方法对于 A-967079 作为治疗剂的进一步开发至关重要，但目前还没有从任何基质中对其进行分析的方法。因此，开发并验证了一种快速、简单的 HPLC-MS/MS 方法来定量兔血浆中的 A-967079。这里介绍的方法具有 25 nM 的优异 LOD 和宽线性范围 (0.05–200 μM)，具有良好的准确度和精密度（分别为 100 ± 10.5% 和 <14.2% 相对标准偏差）。在大多数评估的储存条件下，A-967079 在血浆中的稳定性都非常出色。该方法已成功应用于从治疗动物中测定 A-967079，并且它可能有助于开发这种 TRPA1 拮抗剂作为对抗 TIH 暴露的有害影响的治疗剂。