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目的:建立大鼠血浆吡非尼酮检测的高效液相色谱方法,研究吡非尼酮的药代动力学。方法:血浆经乙酸乙酯,采用ZORBAX SB-C18色谱柱;流动相为乙腈-水-0.1%TFA(三氟乙酸),流速为1.0 mL·min-1;检测波长为318(0～8 min)、246nm(8～10 min)。6只雄性大鼠单剂量灌胃给予15 mg.kg-1吡非尼酮,分别在给药后多点尾静脉采血;用该方法检测血浆中吡非尼酮的浓度。用DAS(数据采集系统)计算药代动力学参数。结果:吡非尼酮浓度在0.025～4.00 mg·L-1范围内线性关系良好(r=0.999 9);定量下限为0.025 mg·L-1;低、中、高3个浓度的相对回收率分别为(100.40±4.66)%、(102.17±4.02)%和(101.12±2.89)%;日内RSD分别为4.6%,3.9%,2.9%,日间RSD分别为5.5%,4.8%,3.7%。大鼠吡非尼酮灌胃后,血浆吡非尼酮在0.39 h达到1.69 mg·L-1的峰值浓度,血浆半衰期为2.21 h。吡非尼酮在大鼠体内符合一级吸收的二室模型。结论:本方法准确可靠、简便快速,适用于大鼠血浆吡非尼酮浓度的测定及其药代动力学研究。
Objective: To establish a HPLC method for the determination of pirfenidone in rat plasma and study the pharmacokinetics of pirfenidone. METHODS: The plasma was eluted with ethyl acetate using ZORBAX SB-C18 column. The mobile phase consisted of acetonitrile-water-0.1% TFA (trifluoroacetic acid) at a flow rate of 1.0 mL · min- ), 246 nm (8-10 min). Six male rats were given a single dose of 15 mg.kg-1 pirfenidone, respectively, after administration of tail vein venous blood sampling; this method was used to detect plasma concentrations of pirfenidone. Pharmacokinetic parameters were calculated using DAS (Data Acquisition System). Results: The linear range of pirfenidone was 0.025 ~ 4.00 mg · L-1 (r = 0.999 9), and the lower limit of quantification was 0.025 mg · L-1. The relative recoveries of low, medium and high concentrations of pirfenidone (100.40 ± 4.66)%, (102.17 ± 4.02)% and (101.12 ± 2.89)%, respectively. The intra-day RSD was 4.6%, 3.9% and 2.9% respectively. The daytime RSD was 5.5%, 4.8% and 3.7% respectively. After intragastric administration of pirfenidone, the plasma pirfenidone peaked at 1.39 mg · L-1 at 0.39 h with a plasma half-life of 2.21 h. Pirfenidone conforms to a two-compartment model of primary absorption in rats. Conclusion: The method is accurate and reliable, simple and rapid, suitable for the determination of plasma pirfenidone concentration and its pharmacokinetics.