丁咯地尔血药浓度的高效液相色谱法测定及其药动学

 目的 建立血清中丁咯地尔浓度的反相离子对高效液相色谱分析方法，并用此法研究了丁咯地尔人体药动学。方法 血样碱化后用二氯甲烷萃取。以甲醇-水-冰醋酸(70∶30∶0.1)，含0.005 mol·L^-1十二烷基硫酸钠（pH4）为流动相，Waters Nova Pak C₁₈（5 μm 150 mm×3.9 mm）色谱柱分离。检测波长278 nm。结果 丁咯地尔在0.05～2 μg·mL^-1浓度范围呈线性，r=0.999 6。最低定量浓度0.025 μg·mL^-1。低、中、高浓度（0.1，0.8，1.6 μg·mL^-1）的方法回收率分别为93.4%，95.0%和98.3%，日间及日内RSD分别＜4%和＜6%。药动学研究表明，口服丁咯地尔国产与进口制剂的药-时曲线符合一级吸收一级消除的二房室模型。结论 此法准确可靠，操作简便，适用于临床药动学研究及血药浓度监测。

Determination of buflomedil in serum by HPLC and study on its pharmacok inetics

OBJECTIVE A reversed ion-pair HPLC method was developed for the determination of buflomedil in human serum.Its pharmacokinetic investigation was studied in healthy volunteers.METHODS The drug in serum was extracted with dichloromethane after alkaline purification, and then detected by UV detector at 278 nm with a C₁₈ 5 μm 150 mm×3.9 mm column.The mobile phase was consisted of 0.005 mol·L^-1 sodium lauryl sulphate in methanol-water-glacial acetic acid (70∶30∶0.1, pH 4) at a flow rate of 1 mL·min^-1.RESULTS The calibration curve was linear within the range of 0.05～2 μg·mL^-1 and the limit of quantitation was 0.025 μg·mL^-1.The average recovery of buflomedil at the concentrations of 0.1,0.8,1.6 μg·mL^-1 was 93.4%,95.0% and 98.3%,respectively.The RSD of the within-day and between-day variation were less than 4% and 6%,respectively.The results showed that the concentration time curves of the two preparation were fitted to a two compartment model with first order absorption and elimination.CONCLUSION This experiment established a simple, sensitive and accurate method for the determination of buflomedil levels in human serum.It is suitable for its pharmacokinetic study and therapeutic drug monitoring.