摘要
目的:建立间尼索地平不同对映体在大鼠血浆、人血浆和牛血清白蛋白中蛋白结合率的测定方法,并计算不同种属血浆蛋白的相关参数。方法:采用平衡透析法测定蛋白结合率,用高效液相色谱法测定血浆中药物总浓度及游离药物浓度。结果:R-与S-间尼索地平的血浆蛋白结合率分别为:大鼠血浆为(97.4±8.2)%、(93.0±13.4)%;人血浆为(90.8±10.5)%、(89.2±9.9)%;牛血清白蛋白为(95.3±8.7)%、(91.0±5.7)%。最低定量下限为0.01ng。结论:在体外间尼索地平不同对映体与大鼠血浆、人血浆和牛血清白蛋白结合率很高,R-间尼索地平的结合率及蛋白结合药物的表观最大能力βp均较S-间尼索地平高。随着药物血浆浓度升高,R-间尼索地平结合率下降,S-间尼索地平结合率升高,均有一定的浓度依赖性。
OBJECTIVE A HPLC method was established to determine the protein binding rates of m-nisoldipine enantiomers in human plasma, rat plasma, bovine serum albumin（BSA）, and to calculative the correlate parameters of rn-nisoldipine enantiomers to different genera plasma proteins. METHODS The binding rates of m-nisoldipine enantiomers with different genera plasma proteins were determined by equilibrium dialysis method. The concentrations of m-nisoldipine enantiomers were assayed by HPLC. RESULTS The binding rates of R-, S-m-nisoldipine with rat, human plasma and BSA were （97. 4 ± 8. 2） %, （93.0 ± 13.4） % ; （90. 8 ± 10. 5） %, （89. 2 ±9. 9）% and （95.3± 8. 7） %, （91.0 ±5. 7）%, respectively. The method was sensitive with a lower limit of quantification of 0. 01 ng in different plasma. CONCLUSION The binding rates of m-nisol- dipine enantiomers to human plasma protein, rat plasma protein and BSA were very high. The plasma protein binding rate and of R-m-nisoldipine was higher than those of S-m-nisoldipine. Moreover the binding rate was inversely proportional to plasma concentration of R-rn-nisoldipine, while the S-rn-nisoldipine was identical.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2011年第3期181-185,共5页
Chinese Journal of Hospital Pharmacy
基金
国家自然科学基金项目(编号:30840098)
河北省自然科学基金资助项目(编号:C2008001073)
关键词
间尼索地平
对映体
蛋白结合率
平衡透析法
高效液相色谱法
m-nisoldipine
enantiomers
plasma protein binding rate
equilibrium dialysis method
high performance liquid chromatography
