超高效液相色谱-串联质谱法测定血清中百草枯及大鼠体内的毒代动力学

Determination of paraquat in serum by ultra performance liquid chromatography tandem mass spectrometry and toxicokinetics of paraquat in rat

目的建立血清中百草枯的超高效液相色谱串联质谱(UPLC-MS/MS)检测方法,应用于大鼠体内毒代动力学研究。方法采用ACQUITY UPLC BEH HILIC柱(2. 1 mm×50 mm,1. 7μm),流动相为乙腈:50 mmol/L甲酸铵-0. 4%甲酸水溶液(40∶60,V/V),在电喷雾正离子源和多反应监测模式下进行血中百草枯的定性定量分析。应用于腹腔注射染毒大鼠体内毒代动力学研究,采用WinNonlin 7. 0一室模型计算毒代动力学参数。结果该方法在0. 3～1000. 0μg/L范围线性关系良好,回收率为89. 0%～107. 7%,相对标准偏差(RSD)为1. 9%～13. 8%(n=6)。毒代动力学参数峰浓度(C_(max))为(46. 50±5. 11) mg/L,达峰时间为0. 167 h,消除半衰期(T_(1/2))为(63. 2±16. 2) h。结论该方法灵敏度高,结果准确,适用于毒代动力学试验中百草枯血清样的分析。

Objective To establish a simple and rapid ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method for the determination of paraquat in serum,and to apply to the toxieokineties of paraquat in rats.Methods The samples separated on ACQUITY UPLC BEH HILIC column (2.1mm ×50mm,1.7μm) with acetonitrile -50mmol/L ammonium formate (0.4% formic acid)as mobile phase. The analytes were analyzed using ESI operating in the positive multiple reaction monitoring (MRM)mode.The method was used in toxicokinetic study in poisoned rat.Toxieokinetic parameters were calculated by WinNonlin 7.0statistical software.Results Paraquat was linear in the range of 0.3-1000.0μg/L,the recovery rate was 89.0%-107.7%,and the relative standard deviation (RSD)1.9%-13.8%(n =6).Toxicokinetic parameters were as follows:C Tmax and T1/2were (46.50±5.11)mg/L,0.167h,(63.2± 16.2)h,respectively.Conclusion This method is highly sensitive,high accuracy and is suitable for the analysis of paraquat in the toxieokinetic study in rats.