高效液相色谱-串联质谱法测定大鼠组织中的吡蚜酮

为研究不同染毒剂量下吡蚜酮原药在大鼠体内的毒代动力学特征，以SD大鼠为研究对象，经口灌胃方式单次染毒，采集不同时间点的动物组织样品，经蛋白沉淀处理后，以吡虫啉为内标，采用高效液相色谱-串联质谱法（HPLC-MS/MS）检测大鼠组织中的吡蚜酮原型。结果表明，吡蚜酮在50~10 000 μg/L浓度范围内，线性关系良好，相关系数大于0.98，批内精密度相对标准偏差小于15%。经口染毒后，吡蚜酮在大鼠体内分布较广，给药10 min后，在主要脏器中均检测到吡蚜酮原型，2 h后在多数组织中吡蚜酮浓度达最高峰，而至144 h，除肝脏外，其他组织中吡蚜酮浓度均降至最低定量限以下。此结果与血浆动力学结果吻合，表明该药物在大鼠体内不会长时间蓄积，安全性较高。

Determination of Pymetrozine in Rat Tissues by HPLC-MS/MS

In order to study the toxicokinetic characteristics of pyridoxine in rats at different doses, SD rats were used as the research object, and single-time exposure was carried out by oral gavage. Animal tissue samples were collected at different time points. After the samples were treated with protein precipitation, the pyridoxine prototype was detected by high performance liquid chromatograpy-tandem mass spectrometry (HPLC-MS/MS) method with imidacloprid as internal standard. The results showed that the linear relationship of pymetrozine is good in the concentration range of 50-10 000 μg/L with the relative coefficient more than 0.98, RSD of intra assay precision is less than 15%. After oral administration, pymetrozine was distributed in all organs of rats. At 10 min, the drug concentration in the lung was the highest, followed by spleen, heart, muscle and brain. Compare the changes of drug concentration in different organ tissues over time, it can be found that the peak time of drug concentration in brain and muscle appeared at 10 min, while in other tissues appeared at 2 h. The peaks were sorted in descending order, and the results were: liver>spleen>heart>lung>kidney>muscle>brain>testis>fat.After the drug concentration peaked, the drug concentration in each organ tissue gradually decreased with time. By 144 h, no pymeidone could be detected in all organs except for a small amount of pymetrozine. This result is consistent with the plasma kinetics results, which proves that the pesticide does not accumulate in rats for a long time and has high safety. The above results indicate that pymetrozine can be widely distributed in various organs of rats, and its dynamic distribution in tissues is basically consistent with the trend in plasma, and the elimination is faster, no accumulation tendency. At the same time, pymetrozine can quickly reach the brain tissue through the blood-brain barrier, or enter the testicular tissue through the blood testis barrier, but by 144 h, it is eliminated to below the minimum detection limit, and it has no teratogenic effects. These results provide a basis for the chronic toxicity of pymetrozine and the dose selection for carcinogenicity studies, and provide data support for its safety evaluation and methodological references for subsequent researchers. In this study only the distribution of pyridoxine prototype in rats was examined, and its metabolites was not able to be detected. It is necessary to develop more precise methods to conduct in deep studies to clarify distribution and excretion of metabolites in animals.