三氯乙烯谷胱甘肽 II 相代谢物的 LC-MS/MS 高灵敏检测及其在帕金森病模型小鼠研究的应用

三氯乙烯(TCE)广泛用于工业清洗，作为环境污染物，其代谢产物已被证实具有肝肾毒性及神经毒性。本文建立和应用高灵敏度LC-MS/MS方法分析TCE与谷胱甘肽(GSH)结合的II相代谢物S-(1,2-二氯乙烯基)-谷胱甘肽(DCVG)、S-(1,2-二氯乙烯基)-L-半胱氨酸(DCVC)和N-乙酰基-S-(1,2-二氯乙烯基)-L-半胱氨酸(NAcDCVC)，该方法展现出良好的线性关系(R >0.999)、较低的检出限(LOD)范围(0.0015—0.0039 nmol·L⁻¹)和定量限(LOQ)范围(0.0051—0.0129 nmol·L⁻¹)，优异的重复性(CV <9%)与准确性(回收率范围为86.95%—114.47%)。方法成功应用在帕金森病(PD)小鼠模型的肝脏和肾脏样本分析并支持PD研究，结果显示：PD小鼠和正常小鼠模型的3个II相代谢物在肝脏和肾脏样品中均有明显差异，提示了PD病理状态可能干扰了TCE的下游代谢。本文建立和应用高灵敏度LC-MS/MS方法分析TCE与谷胱甘肽(GSH)结合的II相代谢物S-(1,2-二氯乙烯基)-谷胱甘肽(DCVG)、S-(1,2-二氯乙烯基)-L-半胱氨酸(DCVC)和N-乙酰基-S-(1,2-二氯乙烯基)-L-半胱氨酸(NAcDCVC)，该方法展现出良好的线性关系(R >0.999)、较低的检出限(LOD)范围(0.0015—0.0039 nmol·L⁻¹)和定量限(LOQ)范围(0.0051—0.0129 nmol·L⁻¹)，优异的重复性(CV <9%)与准确性(回收率范围为86.95%—114.47%). 方法成功应用在帕金森病(PD)小鼠模型的肝脏和肾脏样本分析并支持PD研究，结果显示：PD小鼠和正常小鼠模型的3个II相代谢物在肝脏和肾脏样品中均有明显差异，提示了PD病理状态可能干扰了TCE的下游代谢。

Trichloroethylene (TCE), a widely used industrial solvent, is a pervasive environmental contaminant whose metabolites are linked to hepatotoxicity, nephrotoxicity, and neurotoxicity. We developed and validated a highly sensitive LC-MS/MS method for quantifying key phase II metabolites of TCE: S-(1,2-dichlorovinyl)glutathione (DCVG), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC). The method exhibited excellent linearity (R² > 0.999), low limits of detection (LOD: 0.0015— 0.0039 nmol·L⁻¹) and quantification (LOQ: 0.0051—0.0129 nmol·L⁻¹), and high reproducibility (CV < 9%) with recovery rate: 86.95% —114.47%. Application to liver and kidney tissues from Parkinson’s disease (PD) mouse models revealed significant differences in metabolite levels between PD and control groups, suggesting that PD-associated pathology may disrupt downstream TCE metabolism.