应用3μm填料色谱柱快速分析血清样品和尿样中头孢他啶的浓度及健康人体药动学研究

Pharmacokinetic study and rapid determination of ceftazidime in serum and urine with column packed by 3μm particle

目的:建立快速测定血清和尿样中头孢他啶含量的HPLC法,进行药代动力学研究。方法:采用Alltima C18(53mm×7mm,3μm)色谱柱,流动相为0.02mol·L-1磷酸二氢钾-甲醇(85∶15,v/v),流速为2mL·min-1,检测波长为254nm。结果:血清样品在0.25～50μg·mL-1范围内,尿样在1.25～250μg·mL-1范围内呈现良好的线性关系。对血清样品和尿样,平均回收率分别为95%～115%和102%～105%,日内和日间RSD均小于6.0%。整个分析时间约3min。12名受试者静脉给予1000mg头孢他啶后,获得的主要药代动力学参数为Cmax(70.58±8.23)μg·mL-1,t1/2(1.89±0.57)h,AUC0-24(139.0±19.5)μg·h·mL-1,0～24h尿累计排泄率为(78.9±17.2)%。结论:与5μm填料色谱柱常规分析所需相比,3μm填料的色谱柱可以显著提高测试速度。本方法简便、快速和准确,可用于头孢他啶的药代动力学研究。

Objective ：To establish a rapid HPLC method for the determination of cefiazidime in serum and urine and to study the pharmacokinetics of cefiazidime. Method： Alltima C18 （53 mm×7 mm,3μm） was used as analysis column, mobile phase was 0. 02 mol·L^-1 KH2PO4-methanol （ 85 ： 15, v/v）, flow rate was 2. 0 mL·min^- 1, ultraviolet detector was used with wavelength set at 254 nm. Results：The calibration curves were linear over the range of 0. 25 - 50μg·mL^-1 for serum and 1.25 -250μg·mL^-1 for urine. Average recovery rates were 96% - 115% for serum and 102% - 105% for urine samples. The intra - day and inter - day relative standard deviations were less than 6. 0%. The whole run time was around 3 rain. After 12 subjects were intravenously given 1000 mg of ceftazidime, the main pharmacokinetic parameters were as follows ： Cmax （70. 58±8. 23 ）μg·mL^-1,t1/2 （ 1.89±0. 57） h, AUC0-24 （ 139. 0±19. 5）μg·h·mL^-1 ,accumulative excretion rate of cefiazidime in urine from 0 to 24 h was（78.9±17. 2）%. Conclusion： Compared with that of 5μm particle size, the column packed with 3 μm particle size can significantly reduce the run time. The established method is simple, rapid and accurate for the pbarmacokinetic study of cefiazidime.