反相高效液相色谱法测定兔血清中拉莫三嗪的浓度及其动物药代动力学研究

 用反相高效液相色谱法测定了兔血清中抗癫痫药拉莫三嗪的浓度 ,以苯乙酮作内标 ,甲醇 磷酸二氢钾 ( 0 0 5mol/L ,pH 3 8)为流动相 ,经YWG ODS柱 ( 2 0 0mm× 3 6mmi d )分离 ,波长为 3 0 5nm的二极管阵列检测器检测 ,结果血药浓度在 0 2 5mg/L～ 5 0mg/L范围内线性良好 (r =0 9998) ,平均回收率为 93 78% ,标准误差为2 66% ,日内和日间RSD分别为 2 4 % (n =9)和 5 3 % (n =5 )。取家兔经胃给药 ( 2 5mg/kg) ,在设定时间抽血 ,测定动物药代动力学参数 ,经 3P87药代动力学程序包拟合 ,结果为Cmax=9 3 4 μg/mL ,t1/ 2 (Ke) =8 78h。

Determination of Lamotrigine in the Serum and Study on Pharmacokinetics in Rabbits by RP-HPLC

In the treatment of epileptic patients a method was developed to monitor the lamotrigine concentration by HPLC using a YWG-ODS column and a detector at 305 nm. The linear range was from 0.25 mg/L to 50 mg/L with a mean correlation coefficient of 0.9998. The average recovery was 93.78% and the standard deviation was 2.66%. Within and between-day precisions were 2.4% (n = 9) and 5.3% (n = 5) in RSD respectively. The pharmacokinetics was studied after a single dose of 25 mg/kg for 3 rabbits. Lamotrigine concentrations in serum were assayed and the parameters were computed with 3P87 program. The concentration-time curve of lamotrigine in rabbits fitted to a two compartment model, in which Cmax was 9.34 micrograms/mL, t1/2(Ke) was 8.78 h, and CL/f(s) was 0.69 L/h. The method is rapid, accurate and can be used as routine test in the use of lamotrigine.