HPLC法测定SHR血清中硝苯地平浓度及其药代动力学研究

HPLC DETERMINATION OF NIFEDIPINE IN SERUM AND ITS PHARMACO KINETICS IN SPONTANEOUS HYPERTENSIVE RATS

目的建立血清中硝苯地平浓度的ＨＰＬＣ测定法，研究其在自发性高血压大鼠（ＳＨＲ）体内的药动学。方法ＳＨＲ灌胃给与硝苯地平１０ｍｇ／ｋｇ，用ＨＰＬＣ法测定硝苯地平血清浓度。用乙酸乙酯提取出血清中的硝苯地平，在５０℃水浴中用氮气吹干，残渣用流动相溶解后进样。选用ｓｈｉｍＰａｃｋＣＬＣ－ＯＤＳ柱，甲醇－水（６∶４）作流动相，检测波长２３５ｎｍ。结果：硝苯地平最低检出浓度为０．０２μｇ／ｍｌ，标准曲线线性范围为０．０２～５．０μｇ／ｍｌ（ｒ＝０．９９９７），血样平均回收率为９８．０９％。硝苯地平在大鼠体内的药动学符合一定开放模型，其参数为Ｔ１／２ｋａ＝０．８２８±０．５５ｈ，Ｔ１／２ｋｅ＝３．１７±２．３２ｈ，Ｔｍａｘ＝２．１２±１．４７ｈ，Ｃｍａｘ＝２．７８±１．５０μｇ／ｍｌ和ＡＵＣ＝２４．５±２９．２ｈ·μｇ／ｍｌ。结论本法能满足血清中硝苯地平浓度测定及药动学研究的需要。

Objective To establish a method which can determine nifedipine in serum by HPLC and to study its pharmacokinetics in spontaneous hyper-tensive rats (SHR). Methods Nifedipine was intragastrically given to SHR 10mg/kg HPLC was used to determine concentration of nifedipine in serum. Nifedipine was extracted with ethyacetate from serum and evaperated in 50℃ water bath. The residue was dissolved in mobile phase and injected into Shim-Pack CLC-ODS colum. Nifedipine was detected at 235nm, using 60% methanol as the mobile phase. Results The minimum working concentration of nifedipine was 0.02μ/ml, The standard curve was linear over the concentration range of 0.02-5.0μg/ml(r=0.9997). The mean rate of recovery from serum sample supplemented with nifedipine was 98.09%. The pharmacokinetics of nifedipine was fit to one compartment opened model. The calculated results were: T 1/2ka=1.005±0.55h, T1/2ke=3.17±2.32h Tmax=2.12±1.47h, Cax=2.78±1.50μg/ml and AUC=24.5±29.2hμg/ml. Conclusion This method is satisfactory for determination of nifedipine in serum and study on its pharmacokinetics.