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作为吡非尼酮的类似物,美氟尼酮在临床前研究中显示了良好的抗纤维化活性,具有开发成为新型抗纤维化药物的潜力。本研究建立并验证了测定大鼠血浆中美氟尼酮浓度的高效液相色谱方法。该方法选择吡非尼酮作为内标,采用甲醇沉淀蛋白制备血浆样本。色谱条件:Agilent ZORBAX SB-Aq柱(4.6 mm×250 mm,5μm),流动相10 mM的甲酸铵(添加1.5‰的甲酸调节p H至3.0)–乙腈–甲醇(60:23:17,v/v/v),流速为1.0 mL/min,紫外检测波长为245 nm。美氟尼酮和吡非尼酮色谱峰的保留时间分别为5.5 min和7.8 min。美氟尼酮在0.1–20μg/m L范围内具有良好的线性关系(r~2=0.9997)。本方法的批间和批内准确度偏差为–4.2%~6.5%,批间和批内的精密度均小于8.6%。该方法成功应用于美氟尼酮的大鼠单剂量灌胃和单剂量尾静脉注射给药的药代动力学研究。灌胃给药和尾静脉注射美氟尼酮后,药物在大鼠体内的消除半衰期分别为(3.41±0.81)h和(2.26±0.87)h,其绝对生物利用度为79.1%。
As an analogue of pirfenidone, meronitadione shows good antifibrotic activity in preclinical studies and has the potential to be developed into a new class of antifibrotic drugs. This study established and validated the HPLC method for the determination of the concentration of mefenafil in rat plasma. The method selects pirfenidone as the internal standard and uses a methanol precipitation protein to prepare a plasma sample. Chromatographic conditions: Agilent ZORBAX SB-Aq column (4.6 mm × 250 mm, 5 μm), mobile phase of 10 mM ammonium formate (pH 1.5 adjusted with 1.5 ‰ of formic acid) -acetonitrile-methanol (60:23:17, v / v / v) at a flow rate of 1.0 mL / min with UV detection at 245 nm. The retention times of mefenapyr and pirfenidone were 5.5 and 7.8 min, respectively. In the range of 0.1-20μg / m L, there is a good linear relationship (r ~ 2 = 0.9997). The accuracy of this method was -4.2% ~ 6.5% within batch and batch, with the precision of less than 8.6% in both batches and batches. This method was successfully applied to the pharmacokinetics of single-dose gavage and single-dose tail vein injection in rats receiving metronix treatment. After oral gavage and intravenous injection of metformin, the half-lives of drugs in rats were (3.41 ± 0.81) h and (2.26 ± 0.87) h, respectively, with an absolute bioavailability of 79.1%.