HPLC测定血浆中硝苯地平浓度及在Beagle犬体内的应用

 目的建立血浆中硝苯地平浓度的HPLC分析方法,并用此法检测硝苯地平在Beagle犬体内的药物浓度。方法选择尼群地平为内标,血浆经无水乙醚-正己烷(3:1)提取,采用Hypersil BDS C₁₈(4．6 mm×150 mm,5 μm)色谱柱,以乙腈-水(1:1) (1%磷酸调节pH至3．5)为流动相,流速为1.0 mL·min^-1,紫外检测波长为238 nm。2只Beagle犬服用硝苯地平30 mg后用此法检测其血药浓度。结果硝苯地平在2～200μg·L^-1线性关系良好(r=0．999 6),最低检测限为1μg·L^-1(S/N≥3)。提取回收率为77.6%～87.3%,相对回收率在90.5%～101.7%内;日内精密度RSD≤7.1%,日间精密度RSD≤2.5%。结论本方法简便、准确灵敏,重现性好,可用于硝苯地平的血药浓度分析及进行药动学和生物等效性实验研究。

Determination of Nifedipine in Plasma by HPLC Assay and Application to Pharmacokinetics in Dogs

OBJECTIVE To develop a HPLC method for the determination of nifedipine in plasma and to investigate its pharmacokinetic characteristics in dogs.METHODS Nifedipine and internal standard (nitrendipine) were extracted from plasma with Ethyl ether-n-hexane (3:1) , and then detected by UV detector at 238 nm with C₁₈ column and acetonitrile-water (1:1) (pH3.5) as mobile phase at the flow rate of 1.0 mL·min^-1. The plasma concentration in two dogs was detected by HPLC assay. RESULTS The linear range was 2～200 μg·L^-1 (r=0.999 6) ,the lowest detectable concentration was 1 μg·L^-1.The intra-and inter-day precisions were lower than 6.3% and 4.0% (n=5), respectively. The extraction recovery was 77.6%～87.3% (n=5) and the method recovery was 90.5%～101.7% . Both the intra-and inter-day precisions were less than 10% .CONCLUSION The method is simple, sensitive, accurate and reproducible. It can be used for the pharmacokinetic studies of nifedipe in dogs.