Department of Legal Medicine, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Department of Legal Medicine, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Leg Med (Tokyo). 2023 Nov;65:102323. doi: 10.1016/j.legalmed.2023.102323. Epub 2023 Sep 14.
Fenthion (MPP) is a popular organophosphorus pesticide that acts via inhibition of the enzyme cholinesterase. It is well known that fenthion is metabolized by plants, animals and soil microorganisms to sulfone and sulfoxide by oxidation of thioether and is further metabolized by conversion of P = S to P = O (oxon). Although human fenthion poisonings sometimes occur, details of the distribution of fenthion and its metabolites within the bodies of victims are unclear. In this study, we developed and validated an approach that uses liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to quantify the concentrations of fenthion and its five metabolites (MPP-sulfoxide, MPP-sulfone, MPP-oxon, MPP-oxon sulfoxide and MPP-oxon sulfone) in the fluids [blood, cerebral spinal fluid (CSF) and urine] of a human cadaver. The calibration curves were linear in the concentration range 5-200 ng/mL. Our method allowed for repeatable and accurate quantification with intra- and inter-assay coefficients of variation smaller than 8.6% and 11.0%, respectively, for each target compound. We used the developed method to measure the fenthion concentration in the blood of a dead victim of fenthion poisoning and found the concentration to be in the comatose-fatal range. In addition, we detected for the first time fenthion and all five fenthion metabolites in the cadaveric blood and CSF. The concentrations of the oxidized forms of fenthion, including MPP-sulfone and MPP-sulfoxide, were higher in CSF than in the blood.
倍硫磷(MPP)是一种常用的有机磷农药,通过抑制胆碱酯酶发挥作用。众所周知,倍硫磷在植物、动物和土壤微生物中通过硫醚的氧化代谢为砜和亚砜,进一步通过 P=S 到 P=O(氧代)的转化代谢。虽然人类倍硫磷中毒时有发生,但受害者体内倍硫磷及其代谢物的分布细节尚不清楚。在这项研究中,我们开发并验证了一种使用液相色谱-电喷雾串联质谱法定量分析人尸体体液(血液、脑脊液和尿液)中倍硫磷及其五种代谢物(MPP-亚砜、MPP-砜、MPP-氧代、MPP-氧代亚砜和 MPP-氧代砜)浓度的方法。校准曲线在 5-200ng/mL 的浓度范围内呈线性。我们的方法允许重复和准确地定量,每个目标化合物的日内和日间变异系数均小于 8.6%和 11.0%。我们使用开发的方法测量了一名死于倍硫磷中毒的死者的血液中倍硫磷的浓度,发现浓度处于昏迷-致命范围。此外,我们首次在尸体血液和脑脊液中检测到倍硫磷和所有五种倍硫磷代谢物。氧化形式的倍硫磷,包括 MPP-砜和 MPP-亚砜,在脑脊液中的浓度高于血液。