氯氰菊酯及其代谢物在犬胆汁中的代谢动力学研究

Study on the toxicokinetics of cymermethrin and its metabolites in dog bile

目的研究氯氰菊酯及其代谢物在犬胆汁中的毒物动力学,为氯氰菊酯中毒的法医学鉴定提供实验依据。方法 6只雄性犬胆囊造瘘术后,经口灌胃1/4LD50剂量的氯氰菊酯,于不同时间点收集胆汁,二氯甲烷液液萃取法提取,高效液相色谱-串联质谱仪分析,MRM记录方式,保留时间和定性离子对定性,内标法和标准曲线法定量检测其中氯氰菊酯(CYM)、3-苯氧基苯甲酸(3-PBA)、二氯菊酸(DCVA)含量,Win Nonlin拟合C-T曲线,计算毒代动力学参数。结果经口灌胃1/4LD50氯氰菊酯后,氯氰菊酯及其代谢物在犬胆汁中的毒物动力学过程均符合一级动力学模型,达峰时间分别为1.52±0.30、1.29±0.04、0.93±0.41 h,达峰浓度分别为0.38±0.03、7.9±1.32、30.9±16.24μg/m L,半衰期分别为3.93±0.71、1.36±0.11、4.49±2.81 h。结论经口灌胃后氯氰菊酯及其代谢物3-苯氧基苯甲酸、二氯菊酸的毒物动力学符合一级吸收代谢动力学模型,模型和参数可以为氯氰菊酯中毒的法医学鉴定提供实验依据。

Objective To study the toxicokinetics of Cymermethrin and its metabolites in dog bile and provide evidence for forensic cases of identification of Cymermethrin poisoning.Methods 1/4 LD50 doses of Cymermethrin were given to 6 male dogs by oral perfusion after the gallbladder fistula surgery on them,and their bile were collected at different time,in which Cymermethrin and its metabolites were extracted by Liquid-liquid extraction with dichloromethane and detected by HPLC-MS-MS.The qualitative analysis was based on retention time and MRM ions.The quantitative analysis was based on an internal standard method and calibration curve.Toxicokinetics equations of Cymermethrin and its metabolites in the bile were established from the c-t curves which were fitted by the Win Nonlin toxicokinetics software meanwhie toxicokinetics parameters were obtained.Results The toxicokinetics of Cymermethrin met first-order dynamic equation.The Tmax of Cymermethrin（CYM）,3-phenoxybenzoic acid（3-PBA）,3-（2,2-Dichloroethenyl）-2,2-dimethyl-cyclopropanecarboxylate（DCVA） respectively were 1.52±0.30,1.29±0.04,0.93±0.41 h; The Cmax of CYM,3-PBA,DCVA respectively were 0.38±0.03,7.9±1.32,30.9±16.24 μg/m L; The T1/2 of CYM,3-PBA,DCVA respectively were3.93±0.71,1.36±0.11,4.49±2.81 h; Conclusion The toxicokinetics of Cymermethrin in dog bile met first-order dynamic equation; The toxicokinetics model and parameters of Cymermethrin can provide evidence for forensic identification of Cymermethrin poisoning cases.