西洛他唑的高效液相色谱法测定及药动学研究

目的 建立测定人血浆中西洛他唑含量的高效液相色谱(HPLC) 法, 并研究西洛他唑片在健康人体内的药动学。 方法 色谱柱为Hypersil C18 柱(4.6 mm ×200 mm, 5 μm), 流动相为乙腈-水(45∶55), 流速1.0 ml·min^-1, 柱温30 ℃, 检测波长254 nm, 西洛他唑血浆样品以2 mol·L^-1NaOH-无水乙醚(1∶4) 提取, 以地西泮为内标。 结果 标准曲线线性范围20 ~ 2 000 μg·L^-1 (r=0.9999)。血浆中西洛他唑最低检测限为10 μg·L^-1。平均提取回收率为80.2 % ±3.6 %, 平均方法回收率为97.0 % ±3.8 %, 日内RSD ≤5.8 %, 日间RSD ≤10.1 %。应用该法研究了10 例健康志愿者口服100 mg 西洛他唑后的药动学;其体内过程符合二室模型, t_max 为3.58±1.08 h, C_max 为920 ±230 μg·L^-1, AUC_0-48 为11.0±3.3 mg·h^-1·L^-1。 结论 此法简便、快速, 适用于药物分析, 其药动学数据可为临床合理用药、新药研制及剂型改进提供理论依据。

Determination of cilostazol in human plasma and its pharmacokinetics by HPLC

AIM: To establish a reversed phase highperformance liquid chromatographic method to determine cilostazol in human plasma and to study the pharmacokinetics of cilostazol in 10 healthy volunteers. METHODS: Using diazepam as the internal standard, cilostazol was extracted from human plasma with a mixture of 2mol ·L^-1 NaOH-diethyl ether anhydrous (1:4).The mobile phase was acetonitrile-water (45:55), flow rate 1 ml· min^-1, and the UV absorbance wavelength 254 nm.The pharmacokinetic analysis of cilostazol in 10 healthy volunteers after oral administration of 100mg was studied. RESULTS: Linear range of the standard curve was from 20 to 2 000 μg·L^-1 (r=0.9999).The quantitative limit for cilostazol was 10 μg·L^-1.The mean extraction recovery was 80.2 %±3.6 %.The mean analytical recovery was 97.0 % ±3.8 %.The relative standard deviation of intra-day and inter-day did not exceed 5.8 % and 10.1 %, respectively.It was found to be fitted to a twocompartment open model and its pharmacokinetic parameters were as follow:t_max 3.58 ±1.08 h, C_max 920 ±230 μg ·L^-1 AUC_0-48 11.0 ±3.3 mg·h^-1 ·L^-1, respectively. CONCLUSION: The method is suitable for drug monitoring of cilostazol and the pharmacokinetics of cilostazol in human provides a useful index for clinical trial.