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目的:建立肺炎克雷伯菌(Klebsiella pneumoniae,Kp)肺部感染小鼠模型,采用高效液相色谱(HPLC)法测定不同剂量左氧氟沙星(levofloxacin,LVF)在其体内的药动学参数。方法:血浆样品经乙腈沉淀蛋白后,采用Diamosail-C18色谱柱分离,流动相为乙腈(0.05 mol·L~(-1))-磷酸二氢钾(17∶83),磷酸二氢钾盐溶液以磷酸调整pH为3.0左右,流速为1 mL·min~(-1);检测波长为295 nm。结果:LVF在0.3~12 mg·L~(-1)内线性关系良好;方法的日间和日内精密度均小于7.2%,稳定性良好。Kp肺部感染小鼠口服LVF15,30,60和90 mg·kg~(-1)后,LVF的PK参数tmax、t1/2、CL/F和Vd/F均无显著性差异(P>0.05)。结论:所建立的HPLC分析方法准确、灵敏、专属性强、重复性高,适用于肺炎克雷伯菌肺部感染小鼠体内的左氧氟沙星药动学研究。
Objective: To establish a murine model of pulmonary infection of Klebsiella pneumoniae (Kp) and determine the pharmacokinetic parameters of levofloxacin (LVF) in vivo by high performance liquid chromatography (HPLC). Methods: The plasma samples were separated by Diamosail-C18 column with acetonitrile and the mobile phase consisted of acetonitrile (0.05 mol·L -1) -potassium dihydrogen phosphate (17:83), potassium dihydrogen phosphate Adjust the pH to about 3.0 with phosphoric acid at a flow rate of 1 mL · min ~ (-1) and a detection wavelength of 295 nm. Results: The linearity of LVF in 0.3 ~ 12 mg · L ~ (-1) was good. The intra-day and intra-day precision of LVF were less than 7.2% and the stability was good. There were no significant differences in the PK parameters tmax, t1 / 2, CL / F and Vd / F of LVF in Kp-infected mice after oral administration of LVF15,30,60 and 90 mg · kg -1 ). Conclusion: The established HPLC method is accurate, sensitive, specific and reproducible. It is suitable for pharmacokinetics of levofloxacin in mice with pulmonary infection of Klebsiella pneumoniae.