论文部分内容阅读
为阐明杀虫剂哌虫啶在SD大鼠体内的代谢动力学过程,以期为进一步的毒理学研究提供依据,采用所建立的高效液相色谱-串联质谱(HPLC-MS/MS)分析方法,测定了单次灌胃给药后大鼠血浆、组织(心、肝、脾、肺、肾、脑、骨骼肌、脂肪)、粪便和尿液样品中哌虫啶的含量,对该药在大鼠体内的吸收、分布和排泄进行了研究。结果表明:哌虫啶750 mg/kg单次经口灌胃给药,雌性大鼠血药浓度-时间曲线下面积(AUC)高于雄性大鼠,且达到峰值时间(T_(max))明显长于雄性大鼠,具有统计学差异,提示在此剂量下,哌虫啶在代谢及毒性效应上可能存在性别差异;在100~750 mg/kg受试剂量范围内,哌虫啶的平均半衰期为4~8 h,表观分布容积为10~30 L/kg,给药剂量与血药浓度-时间曲线下总面积(AUC_(0-inf))呈线性相关性(雄:r=0.996 4,雌:r=0.991 3)。组织分布试验表明,哌虫啶经口给药后,能迅速、广泛地分布到各组织中,并可有效地透过血脑屏障,其中肝、肾中哌虫啶的含量最高,提示其可能主要经肝、肾代谢。排泄试验显示,经尿液及粪便排出的原形哌虫啶含量极低,提示哌虫啶在大鼠体内可能发生广泛的代谢后再排出体外。
In order to clarify the metabolic kinetics of insecticides and insects in SD rats, in order to provide a basis for further toxicological studies, using established by high performance liquid chromatography - tandem mass spectrometry (HPLC-MS / MS) The content of pipemidine in the plasma, tissue (heart, liver, spleen, lung, kidney, brain, skeletal muscle and fat), feces and urine samples of rats after single gavage administration was determined. Absorption, distribution and excretion in the rat were studied. The results showed that the area under the blood concentration-time curve (AUC) was significantly higher than that of the male rats at the dose of 750 mg / kg. The peak time (T max) was significantly Longer than male rats, with statistical differences, suggesting that at this dose, there may be sex differences in the metabolic and toxic effects of pipemidine; in the range of 100-750 mg / kg doses, the average half-life of pipemidine is 4 ~ 8 h, the apparent volume of distribution was 10 ~ 30 L / kg, and the dose was linearly correlated with the total area under the plasma concentration-time curve (AUC_ (0-inf) Female: r = 0.991 3). Tissue distribution test showed that, after oral administration, the worm could be rapidly and widely distributed in various tissues and could effectively penetrate the blood-brain barrier, and the highest content of pipemidine was found in liver and kidney, suggesting that it may Mainly by the liver, kidney metabolism. Excretion test showed that urine and excreted by the urine of the original form of very low content of piperidine, suggesting that in the body of the United States may have widespread metabolism and then excreted.