兔血浆利福平的反相高效液相色谱分析及药代动力学研究

RP-HPLC Determination and Pharmacokinetic Study of Rifampicin in Rabbit Plasma

目的建立兔血浆利福平（rifampicin,RFP）反相高效液相色谱分析方法（reversed-phase high-performance liquid chromatography,RP-HPLC）。研究其静脉给药后兔体内血浆药代动力学参数。方法以Agilent ZORBAX XDB-C18柱（5μm,4.6mm×150mm）为分析柱,流动相为0.02mol·L^-1磷酸二氢钠缓冲液（PH7.0）∶甲醇=30∶70;流速1.0mL·min^-1;柱温：35℃,检测波长330nm。8只新西兰大白兔分别按RFP12mg·kg^-1静滴,RP-HPLC法检测血浆药物浓度。所得血药浓度数据经DAS软件拟合分析。结果 RFP在0.5～72μg·mL^-1血浆浓度范围内线性关系良好（r=0.99969）,平均提取回收率为99.72%,日内、日间变异系数（RSD=5）分别为2.6%～4.4%和2.2%～2.9%。静脉滴注RFP在兔体内药代动力学过程符合双隔室模型（权重系数为1/cc）,T1/2=（2.87±0.78）h,Cmax=（12.49±1.57）mg·L^-1,AUC（0-∞）=（50.05±14.50）mg·（h·L）^-1。结论本研究建立的兔血浆利福平RP-HPLC方法简便、准确、重现性好,可用于兔体内利福平血药浓度的测定,兔体内利福平药代动力学过程符合双隔室模型,体内药代谢动力学参数为利福平其它剂型的研究提供参考。

Objectiye To develop a method for determination of rifampicin （RFP） in plasma samples by reversed -phase high- performance liquid chromatography（ RP- HPLC） and to explore the pharmacokinetic of RFP in rabbits. Methods RP - HPLC was carried out on a Agilent ZORBAX XDB - C18 column（5μm,4.6mm×150mm） using 0.02mol· L^-1 phosphate buffer methanol （30： 70, adjusted pH to 7.0） at 1.0 mL · min^-1. The plasma were analyzed at 330 nm wavelength after methanol protein precipitation. 8 New Zealand white rabbits were injected intravenously by 12mg · kg^-1 INH . Plasma concentration data obtained were fitted by DAS software. Results There was a good linear relationship within the range of 0.5 - 72μg · mL^-1 （ r = 0. 99969）. The extraction recovery was 99.72%. The precsion of intro - day and inter - day was 2.6% 4.4% and 2.2% -2.9% ,respectively. RFP pharmacokinetics in rabbits process was in line with double compartment model（ weighting factor for the 1/cc）, T1/2 = （2.87 ± 0. 78 ） h, Cmax = （ 12.49± 1.57 ） mg · L^-1, AUC（0-∞） = （50.05 ± 14.50） mg·（h · L）^-1. Conclusion This method is simple, accurate, reproducible, and suitable for the determination of pharmacokinetics rifampicin in rabbit plasma. RFP pharmacokinetics in rabbits process in line with double compartment model , In vivo drug of pharmacokinetics provide the reference to the research of rifampicin other dosage forms.