法医学杂志

• 论著 •    

虫螨腈及其代谢物在大鼠体内的毒物代谢动力学

李文艳1,2,3(), 赵晋峰4, 刘唯琛1,2,3, 吕诗婧1,2,3, 张佳欣1,2,3, 张旭东1,2,3, 尉志文1,2,3, 贠克明1,2,3, 张潮1,2,3()   

  1. 1.山西医科大学法医学院,山西 晋中 030600
    2.山西省法医学重点实验室,山西 晋中 030600
    3.法庭毒物分析公安部重点实验室,山西 晋中 030600
    4.晋中市公安局,山西 晋中 030600
  • 收稿日期:2024-03-01
  • 通讯作者: 张潮
  • 作者简介:李文艳(1996—),女,硕士研究生,主要从事法医毒物分析研究;E-mail:Lwy15935110892@163.com
  • 基金资助:
    国家重点研发计划资助项目(2021YFF0602504);国家自然科学基金重点项目(82130056)

Toxicokinetics of Chlorfenapyr and Its Metabolites in Rats

Wen-yan LI1,2,3(), Jin-feng ZHAO4, Wei-chen LIU1,2,3, Shi-jing LÜ1,2,3, Jia-xin ZHANG1,2,3, Xu-dong ZHANG1,2,3, Zhi-wen WEI1,2,3, Ke-ming YUN1,2,3, Chao ZHANG1,2,3()   

  1. 1.School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China
    2.Shanxi Key Laboratory of Forensic Medicine, Jinzhong 030600, Shanxi Province, China
    3.Key Laboratory of Forensic Toxicology, Ministry of Public Security, Jinzhong 030600, Shanxi Province, China
    4.Jinzhong Municipal Public Security Bureau, Jinzhong 030600, Shanxi Province, China
  • Received:2024-03-01
  • Contact: Chao ZHANG

摘要:

目的 建立血液中虫螨腈及其代谢物溴代吡咯腈的色谱-串联质谱检测方法,研究其在大鼠体内的毒物代谢动力学。 方法 大鼠经口灌入虫螨腈(8 mg/kg),于给药后5 min、15 min、30 min、1 h、3 h、6 h、12 h、24 h、48 h经内眦静脉取血,血液样品经100 μL 5%甲酸水溶液和400 μL乙腈提取后,分别使用三重四极杆气相色谱-质谱联用仪对虫螨腈、三重四极杆液相色谱-质谱联用仪对溴代吡咯腈进行定性、定量检测,使用DAS 3.0软件拟合动力学方程并计算其毒物代谢动力学参数。 结果 虫螨腈的检测窗口为5 min至24 h,达峰时间为1 h;溴代吡咯腈的检测窗口为15 min至48 h,达峰时间为3 h。虫螨腈原体在大鼠血液中的的毒物代谢动力学过程符合一级吸收一室开放模型,毒物代谢动力学方程为C=e -0.265t-e -0.175t;溴代吡咯腈符合一级吸收三室开放模型,毒物代谢动力学方程为C=47361.069e -2.209t-35404.962e -1.486t+11956.363e -0.512t。式中,C为血液中目标物的浓度,e为自然常数(≈2.718 28),t为时间。 结论 本研究优化了血液中虫螨腈及其代谢物溴代吡咯腈的检测方法,两者的代谢动力学方程和参数可以为虫螨腈口服入体时间的推断提供参考。

关键词: 法医学, 毒物分析, 毒物代谢动力学, 虫螨腈, 溴代吡咯腈, 气相色谱-质谱法(GC-MS), 液质色谱-质谱法(LC-MS), 大鼠

Abstract:

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood, and to investigate the toxicokinetics in rats. Methods Chlorfenapyr (8 mg/kg) was administered orally to rats, and blood samples were collected from rats’ canthus vein at 5 min, 15 min, 30 min, 1 h, 3 h, 6 h, 12 h, 24 h and 48 h after administration. The blood samples were extracted using 100 μL of 5% formic acid solution and 400 μL of acetonitrile. Chlorfenapyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry (GC-MS/MS) and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry (LC-MS/MS). The DAS 3.0 software was used to fit the toxicokinetic equations and calculate the metabolic kinetic parameters. Results Chlorfenapyr was detectable from 5 min to 24 h and with a peak time of 1 h. Tralopyril was detectable from 15 min to 48 h and with a peak time of 3 h. The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model, with the toxicokinetic equation described as C=e -0.265t-e -0.175t . Tralopyril conformed to the first-order absorption three-chamber model, and the toxicokinetic equation was C=47361.069e -2.209t-35404.962e -1.486t+11956.363e -0.512t . In the equations, C stands for the concentration of the target substance in the blood, e is the natural constant (≈2.718 28), and t stands for time. Conclusion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood. The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

Key words: forensic medicine, toxicological analysis, toxicokinetics, chlorfenapyr, tralopyril, gas chroma-tography-mass spectrometry (GC-MS), liquid chromatography-mass spectroscopy (LC-MS), rats

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