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目的利用液相色谱-质谱(LC-MS)技术测定R-间尼索地平及S-间尼索地平与不同血浆蛋白的结合率。方法采用平衡透析法测定血浆蛋白结合率,LC-MS测定R-间尼索地平及S-间尼索地平的血药浓度及游离药物浓度,样本萃取采用正己烷-乙醚(1∶1)。结果 R-间尼索地平及S-间尼索地平在低、中、高3种浓度下,在鼠血浆、人血浆和牛血清白蛋白中的蛋白结合率均在80%以上,且R-间尼索地平及S-间尼索地平与大鼠血浆的蛋白结合率最高。结论采用LC-MS技术对R-间尼索地平和S-间尼索地平进行测定,方法简单、灵敏度高、结果可靠。R-间尼索地平和S-间尼索地平均属于血浆蛋白高度结合型药物,且蛋白结合率随着药物浓度的增加呈明显的浓度依赖性。
Objective To determine the binding of R-nisoldipine and S-nisoldipine to different plasma proteins by liquid chromatography-mass spectrometry (LC-MS). Methods The plasma protein binding rate was determined by equilibrium dialysis. The plasma concentrations and free drug concentrations of R-nisoldipine and S-nisoldipine were determined by LC-MS. The sample was extracted with n-hexane (1: 1). Results The protein binding rates of R-nisoldipine and S-nisoldipine in rat plasma, human plasma and bovine serum albumin were both above 80% at low, medium and high concentrations, and R- Nisoldipine and S-nisoldipine had the highest protein binding rates to rat plasma. Conclusion The method of LC-MS for the determination of R-nisoldipine and S-nisoldipine is simple, sensitive and reliable. Both R-nisoldipine and S-nisoldipine belong to the high plasma protein-binding drugs, and the protein binding rate is obviously concentration-dependent with the increase of the drug concentration.