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目的建立测定血浆中沙利度胺的方法。方法以非纳西丁为内标,血浆样品用含2%乙酸的乙腈去蛋白处理后进行HPLC测定。色谱柱Agilent Zorbax Eclipse×DB-C8(4.6×150mm,5μm);流动相为10mm乙酸铵溶液-乙腈(72:28,v/v);流速1ml·min-1;室温;进样量20μl;检测波长225nm。结果在0.5～20μg·ml-1范围内,沙利度胺浓度与峰面积比的线性关系良好(R2=0.9997),血浆平均回收率是96.4%,血浆沙利度胺浓度在0.5、2、10μg·ml-1的日内RSD分别为2%～4.4%、1.4%～3.3%和1.5%～2%,日间RSD分别为7.2%、4.4%和1.6%,最低检测限为0.03μg·ml-1。大鼠静脉注射沙利度胺后体内血药浓度-时间曲线符合二室模型,雌雄大鼠体内基本动力学行为相同,t1/2α为1.48～2.8min,t1/2β为159.8～165min,表观分布容积Vd为0.76～0.781L·kg-1,体内消除慢,CLs为0.0032～0.00339L·kg-1·min-1。结论建立了沙利度胺在血浆中HPLC分离测定的方法,该方法灵敏、准确、重复性好、选择性强,适用于大鼠体内药代动力学研究。
Objective To establish a method for the determination of thalidomide in plasma. Methods Non-nalidixin was used as an internal standard, and plasma samples were treated with acetonitrile containing 2% acetic acid for deproteinization. The column was Agilent Zorbax Eclipse × DB-C8 (4.6 × 150 mm, 5 μm); the mobile phase was 10 mm ammonium acetate solution-acetonitrile (72:28, v / v); the flow rate was 1 ml · min- Detection wavelength of 225nm. Results In the range of 0.5 ~ 20μg · ml-1, the linear relationship between the concentration of thalidomide and the peak area ratio was good (R2 = 0.9997), the average recovery rate of plasma was 96.4%, the plasma thalidomide concentration was 0.5, The intra-day RSD of 10μg · ml-1 was 2% -4.4%, 1.4% -3.3% and 1.5% -2% respectively. The daytime RSD was 7.2%, 4.4% and 1.6% respectively. The lowest detection limit was 0.03μg · ml -1. After intravenous administration of thalidomide, the in vivo concentration-time curve of thalidomide conformed to the two-compartment model. The basic kinetic behavior of the rats in both male and female rats was similar. The t1 / 2α was 1.48-2.8min and the t1 / 2β was 159.8-165min. The distribution volume Vd was 0.76 ~ 0.781 L · kg-1, the body elimination slow, CLs 0.0032 ~ 0.00339L · kg-1 · min-1. Conclusion The method for the determination of thalidomide in plasma by HPLC was established. The method is sensitive, accurate, reproducible and selective and is suitable for the study of pharmacokinetics in rats.