高效液相色谱法测定兔血浆中二乙三胺五醋酸浓度及其药物动力学

Pharmacokinetic Study of Serum Diethylenetriaminepentaacetic Acid in Rabbits with HPLC

建立用反相高效液相色谱法测定血浆中二乙三胺五醋酸(DTPA)浓度的方法,DTPA与内标物(烟酸)峰面积之比在DTPA 30～600μg/ml范围内呈直线关系(r=0.9994),回收率为97.4％,样品检出灵敏度为4μg/kg。家兔静脉注射及皮下注射DTPA的药—时曲线符合一室开放模型,按一级动力学消除。DTPA的药动学参数(x±s)皮下注射100mg/kg t_(1/2)。15±2.9min,t_(1/2)53.8±18min,Tmax 44±8min,Cmax274±115μg/ml,V.C/F 0.27±0.15L/kg。DTPA静脉注射50mg/kg t_(1/2) 29±3min,Vd 0.13±0.03L/kg,F 71.3％。

The concentraction of diethylenetriaminepentaacetic acid (DTPA) in rabbits blood plasma was determined by HPLC. Nicotinic acid was used as internal standard marker. Separation of the assayed compounds was made available by using an U Bondpark C_(18) column. The mobile phase was a mixture of 5% methanol and 0. 2 mol/L NaAc-HAc buffer (pH 4. 61). DTPA has its adsorbance at wavelength 254 nm. Under the described condition the retention times for DTPA and Nicotinic acid were approxi- mately 7. 8 and 9. 2 min respectively. Plasma concentration of DTPA was measured in six rabbits at difference time after intravenous injection of DTPA 50 mg/kg and subcutaneous injection of DTPA 100mg/kg. The pharmacokinetic parameters were calculated by using PKBP-Ni computer program. A better curve of plasma concentration-time fitting to a linear of one-compartment open model was obtained. The pharmacokinetic parameters of intravenous injection were: t_(1/2)=29±3min, Vd=0. 13 ±0. 03 L/kg^(-1), AUC=18. 79±4. 7mg/ml·min and subcutaneous injection were: t_(1/2a)=15±2. 9 min, t_(1/2)=53. 8±18min, Tmax=44±8min, Cmax=274±115μg/ml, Vc/f=O. 27±0. 15 L/kg, AUC=26. 79±12. 9mg/ml·min, F=71.3%.