| The widely-used herbicide 2,4 Dichlorophenoxyacetic acid(2,4-D)is selective and low toxicity and used to control many types of broadleaf weeds.We describe a high-performance liquid chromatography(HPLC)with UV detection method for the determination of 2,4-D in biological samples,and aim at investigating the toxicokinetic profile,tissue distribution and excretion of 2,4-D in Sprague-Dawley rats and providing evidence for further study of the herbicide and safety evaluation.The main content is as following:1.The development of method for determination of 2,4-D in biological samplesAccording to the 2,4-D chemical properties,we changed the proportion of the mobile phase,UV detection wavelength,column temperature and flow rate to fine a suitable condition to determinate the concentration of the 2,4-D in biological samples.The lowest limit of quantification is 0.3 ?g/m L;the recovery rate was 100.4% to 108.92%.The method conforms to all requirements of methodology and it found to be specific,precise,reproducible,rapid and low cost.2.The toxicokinetic study of 2,4-D in ratsThe method was applied to determine 2,4-D following oral administration of 2,4-D at 300 mg/kg bw and 60 mg/kg bw in rat.Serial blood samples were collected via eyeground puncture before dosing and at the following intervals,5,15,30 minutes and 1,2,4,8,24,48,72 and 168 hours after dosing.The data was analyzed by DAS 2.1.The serum drug-time curve was consistent with a one-compartment model.The drug elimination half-life(t1/2)were 16.60 ± 13.9 h and 6.84±3.48 h,the time to peak(Tmax)were 17.5 ± 9.06 and 5.25 ± 2.38 h,the Cl/F were 0.10 ± 0.16 ? 0.02 ± 0.01(L/h/kg),respectively.After oral administration,the diffuse of 2,4-D was rapid,and elimination is slow.The AUC with dose increases and has a positive correlation.3.The study of tissue distributionThe method was applied to determine 2,4-D following oral administration of 2,4-D at 300 mg/kg bw and 60 mg/kg bw in rat tissues.The concentrations of 2,4-D in different tissues(brain,lungs,heart,liver,spleen,kidneys,fat,muscle and testicular)were detected by HPLC.The 2,4-D was detected after oral administration in 0.5 h in most tissues,the highest concentration is in the kidney and liver,hint that the kidney and lung may be the target organs.The 2,4-D concentrations in most tissues were reduced after 8 h.The 2,4-D distribute in the brain and testis,hint that 2,4-D can pass the blood brain barrier and blood testosterone barrier.4.The study of excretionSprague-Dawley rats were divided into two groups(three female rats and three male rats of each)and homed in metabolic cages.The feces and urine were collected at 0-5 h,5-24 h,24-48 h,48-72 h and 144-168 h after oral administration of 2,4-D(300 mg/kg bw and 60 mg/kg bw).The concentrations of 2,4-D in these biological samples were detected by HPLC after special treatment.There is more than 3.13% of the 2,4-D excretes through the urine after oral administration in 5 h;Within 24 h,the 2,4-D concentration can also be detected in feces,but is significantly less than it in the urine;Within 168 h,there is still a little 2,4-D excretes from the fece and urine.The 2,4-D in rats is mainly excretd through the urine. |
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