Toxicokinetics Characterization Of N-phenyl-phthalamic Acid In Rat

Objective: N-phenyl-phthalamic acid is a kind of new plant growth regulators of low toxicity. It has been widely used in agriculture recent years. Our study analyze the transport process of N-phenyl-phthalamic acid in rats. And explore the toxicokinetics, distribution and elimination in rats. In order to confirm the target organ, to assess the toxic effect on body of N-phenyl-phthalamic acid, and to provide experimental data for further mechanism research.Methods:1. Establish the HPLC method of N-phenyl-phthalamic acid in biological tissue samples. Optimize and evaluate the established method.2. After a single dose of 2500 mg/kg N-phenyl-phthalamic acid by gavage, detect the content in blood of rats following the different time, evaluate by non-compartmental model and calculate the kinetic parameter.3. Observe the distribution of N-phenyl-phthalamic acid in main organs and dynamic change trend following the time.4. Observe the excretion of N-phenyl-phthalamic acid, detect the content of it in feces and urine following the different time, and analyze the main way of excretion.5. Explore the effect on the organization structure and anti oxidant system of kidney and spleen by N-phenyl-phthalamic acid.Results:1. The verification result of detection method: The RSD of inter-day and intra-day precision was blow 2%. The RSD of reproducibility and stability was below 5%. The recovery of samples was 85.2%~97.5%. The LOD of urine and other samples were 0.2 and 0.5?g/m L, the LOQ were 0.7 and 1.6?g/m L, respectively.2. The concentration-time curves of blood drug was double peak phenomenon. The main kinetic parameters were below: T1/2ka=15 h, Cmax=141.48 mg/L, Tmax=0.68 h, t1/2?=0.22 h, Vz/F=17.54 L/kg, t1/2z=7.77 h.3. After gavage, the N-phenyl-phthalamic acid could be detected in every tissues in rats in 24 h. The tissues from high-content to low-content were: kidney>lung>liver>heart >spleen>muscle>testis>fat>brain. The highest concentration of N-phenyl-phthalamic acid was in kidney, and DTE was 4.77. Suggest that kidney for N-phenyl-phthalamic acid with high affinity. Autopsy results show that the benzene peptide amino acid could cause the spleen damage.4. The total content of N-phenyl-phthalamic acid in feces was 1.45%. The N-phenyl-phthalamic acid was not detected in urine. Prompt only a small number of benzene amino acid peptide to prototype through faeces.5. The different content of N-phenyl-phthalamic acid did not lead to pathologic change in kidney. There was not pathologic change in spleen at first. With the time pass, the number of germinal center decreased. The MDA, T-SOD and GSH in blood, kidney and spleen were influenced by the content of N-phenyl-phthalamic acid.Conclusion:Our study established quick, simple and economical detection method, and the method met the requirements of the experiment. The results of our kinetic study show that, the N-phenyl-phthalamic acid concentration-time curve in serum was double peak phenomenon, which implied that there was im-hepatic circulation phenomenon in rats. N-phenyl-phthalamic acid was soon absorbed and wide distributed. The targeted distribution coefficient of kidney was 4.77, but we did not detected the N-phenyl-phthalamic acid in urine. There was not lesion in glomerulus, which implied that the kidney had relatively high selectivity to N-phenyl-phthalamic acid. And N-phenyl-phthalamic acid could damage the balance of antioxidant system in blood, kidney and spleen in different degree.