Methomyl, (E,Z)-methyl N-{[(methylamino)carbonyl]oxy}ethanimidothioate, is a widely used pesticide that has been detected in many fatal cases of accidental exposure or suicide. Forensic toxicologists have been baffled that the blood methomyl concentration in persons who have died of methomyl poisoning is much lower than the expected concentration in blood. In this study, we speculated two mechanisms underlying the insufficient recovery of methomyl in blood. First, methomyl is decomposed by serum albumin as esterase. Second, methomyl is bound to a specific blood protein, resulting in insufficient recovery in the free form. However, human serum albumin does not show esterase activity for the decomposition of methomyl. On the contrary, specific methomyl hemoglobin adducts have been detected by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). The mass spectra indicated that methomyl was specifically bound to tryptophan (W), tyrosine (Y), and valine (V) residues in hemoglobin. The amounts of W- and V-adducts dose-dependently increased in vitro when the methomyl concentration was lower than the lethal concentration. In addition, the W-adduct was detected in blood sampled from an autopsied subject who died of intentional methomyl ingestion, suggesting that the W-adduct could be used as a biomarker of methomyl poisoning. We were able to estimate the amount of methomyl ingested on the basis of the amount of the W-adduct.

中文翻译：

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血中灭多威死后血红蛋白变化

灭多威, ( E , Z )-甲基N-{[(甲氨基)羰基]氧基}乙氨基硫代酸酯是一种广泛使用的杀虫剂，已在许多意外接触或自杀的致命案例中检测到。法医毒理学家感到困惑的是，死于灭多威中毒的人的血液中灭多威浓度远低于预期的血液浓度。在这项研究中，我们推测了血液中灭多威回收不足的两种机制。首先，灭多威被血清白蛋白作为酯酶分解。其次，灭多威与特定的血液蛋白质结合，导致游离形式的回收不足。然而，人血清白蛋白不显示分解灭多威的酯酶活性。相反，已通过液相色谱四极杆飞行时间质谱 (LC-Q/TOF-MS) 检测到特定的灭多威血红蛋白加合物。质谱表明灭多威与血红蛋白中的色氨酸 (W)、酪氨酸 (Y) 和缬氨酸 (V) 残基特异性结合。W-和V-加合物的量呈剂量依赖性增加体外当灭多威浓度低于致死浓度时。此外，从一名因故意摄入灭多威而死亡的尸体解剖样本中检测到 W-加合物，表明 W-加合物可用作灭多威中毒的生物标志物。我们能够根据 W-加合物的量估计摄入的灭多威的量。