人血清中地尔硫高效液相色谱法测定及药代动力学参数

 建立了反相高效液相色谱法监测人口服地尔硫艹卓缓释片后血药浓度。血样用正己烷－氯仿－异丙醇混合溶剂（６０４０５）提取后，以Ｃ１８化学键合硅胶为固定相，甲醇－水－三乙胺为流动相，安定为内标，在２３９ｎｍ波长处定量检测。血药浓度在１５～３００μｇ／Ｌ范围内线性关系良好，最低检测浓度为３μｇ／Ｌ。批内（ｎ＝７）及批间（ｎ＝５）测定相对标准偏差分别小于６．８％和８．４％，回收率为９１％～１０４％。监测了８名健康人口服盐酸地尔硫艹卓缓释片后的不同时间的血药浓度变化，计算了有关的药代动力学参数。

HPLC determination of diltiazem in human serum and its pharmacokinetic parameters]

A simple and sensitive reversed-phase liquid chromatographic method has been developed and validated for the analysis of diltiazem in human serum and the study of pharmacokinetics of the drug in human body. Diltiazem and diazepam (internal standard) in serum were extracted with hexane-chloroform-isopropanol (60:40:5, V/V), and then measured by HPLC using a Spherisorb C18 column as stationary phase and a methanol-water triethylamine as mobile phase. Diltiazem was quantified by ultraviolet absorbance at 239 nm. The method proved to be linear in the clinical range of 15-300 microg/L with a regression coefficient of 0.9997. The lower limit of detection of diltiazem in serum was 3 microg/L. Intra-day and inter-day coefficients of variation of assay for diltiazem in serum were 3.5%-6.8% (n=7) and 6.2%-8.4% (n=5), respectively. The recoveries of diltiazem were 91%-104% for serum. The method has been used to determine diltiazem in serum samples from eight volunteers and provided data on the pharmacokinetics of the drug. The results inferred that diltiazem is absorbed rapidly and had a relatively short half-life time in healthy individuals. The data obtained was fitted with PKBP-N1 program on computer to study the pharmacokinetics. The results showed that the peak level in serum averaged 118.5 microg/L +/- 14.3 microg/L at 3.1 h +/- 0.4 h, and the areas under the drug concentration curves (AUC) was 793.1 microg x h/L +/- 83.1 microg x h/L.