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 Cmax and a longer Tmax 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 AUC0-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.