高效液相色谱-串联质谱法研究哌虫啶在大鼠体内的吸收、分布及排泄

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。

Investigation of absorption,distribution and excretion of insecticide paichongding in rats by high performance liquid chromatography-tandem mass spectrometry techniques

For further understanding of the toxicity of paichongding(IPP), the pharmacokinetic profile including absorption, distribution and excretion of IPP in rat was investigated. The concentration of IPP in rat plasma, tissues including heart, liver, spleen, lung, kidney, brain, skeletal muscle and fat,and feces as well as urine samples after single oral dose was determined by high performance liquid chromatography-tandem mass spectrometry techniques(HPLC-MS/MS). Results showed that slightly higher AUC(area under the curve) and C_max and a longer T_max in female than male rats were observed with statistical difference after a single oral dose of IPP at 750 mg/kg, which indicated that there were sex differences in metabolism and potential toxicity of IPP in rats. Following oral administration from 100 to 750 mg/kg, the mean half life was from 4 to 8 h and the apparent distribution volume was from 10 to 30 L/kg. The AUC_0-inf showed a dose-proportional increase(male:r=0.9964, female:r=0.9913). The tissue distribution results showed that IPP was rapidly and widely distributed to various tissues and could effectively cross the blood brain barrier in rats following a single oral dose. Relatively high concentrations were found in liver and kidney, suggesting these two organs may play a dominant role in the metabolism of this compound. The excretion data implies that a very low proportion of IPP was excreted as its unchanged form in urine and feces, indicating that IPP could be extensively metabolized in the body.