论文部分内容阅读
目的建立测定人血浆中氟罗沙星浓度的高效液相色谱方法,并用于其药代动力学研究。方法氟罗沙星血浆样品经甲醇沉淀蛋白后直接进样。色谱柱为Diamonsil C18柱,流动相为1%三乙胺(磷酸调pH至4.8)/乙腈(80/20,V/V),流速1.0mL·min–1。采用荧光检测器,激发波长290nm,发射波长458nm。氟罗沙星药代动力学研究采用双周期交叉试验设计。结果氟罗沙星血浆浓度在0.025~8.00μg·L–1范围内线性关系良好,低、中、高浓度质控样品的日内、日间精密度不超过5.16%,方法精密度99.1%~100.9%,提取回收率86.7%~92.0%。健康志愿者口服400mg氟罗沙星试验及参比制剂后主要药代动力学参数分别为:Cmax5.08±0.78和5.38±1.40μg·mL–1,tmax1.72±0.79和1.82±0.78h,t1/211.68±1.27和11.38±1.51h–1,AUC0-∞78.44±11.44和76.53±13.24μg·mL–1·h。结论该方法灵敏度高、定量准确,适用于氟罗沙星人体药代动力学研究。
Objective To establish a HPLC method for the determination of fleroxacin in human plasma and to study its pharmacokinetics. Methods The fleroxacin plasma samples were directly injected after methanol precipitated protein. The column was a Diamonsil C18 column with a mobile phase of 1% triethylamine (adjusted to pH 4.8 with phosphoric acid) / acetonitrile (80/20, V / V) at a flow rate of 1.0 mL · min -1. Using fluorescence detector, excitation wavelength 290nm, emission wavelength 458nm. The pharmacokinetics of fleroxacin was designed using a two-cycle crossover trial. Results The plasma concentration of fleroxacin showed good linearity in the range of 0.025-8.00 μg · L-1. The precision of day, day and day of low, medium and high quality control samples did not exceed 5.16%. The precision of the method was 99.1% -100.9% Extraction recovery rate of 86.7% ~ 92.0%. The main pharmacokinetic parameters of fleroxacin 400 mg and reference preparations after oral administration of 400 mg of fleroxacin to healthy volunteers were: Cmax 5.08 ± 0.78 and 5.38 ± 1.40 μg · mL -1, tmax 1.72 ± 0.79 and 1.82 ± 0.78 h, t1 / 211.68 ± 1.27 and 11.38 ± 1.51 h-1, AUC0-∞78.44 ± 11.44 and 76.53 ± 13.24 μg · mL-1 · h, respectively. Conclusion The method is sensitive, accurate and suitable for the study of human pharmacokinetics of fleroxacin.