Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China.
Drug Dev Ind Pharm. 2010 Mar;36(3):307-14. doi: 10.1080/03639040903154192.
We did a prospective study to investigate the binding of stilbene glucoside (2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside, TSG) to plasma, albumin, and alpha1-AGP (2.0, 10.0, or 50 microg/mL) by three different methods: ultrafiltration, equilibrium dialysis and cloud-point extraction (CPE).
Drug stability in plasma was assessed at different temperatures (4, 25, and 37 degrees C) and on the condition of thawing and freezing. A previously validated high-performance liquid chromatography (HPLC) method was used to analyze the total concentration of drug and free fraction in the samples.
The binding of TSG to plasma increased with adding drug concentration. The binding to albumin was constant (about 60%) within concentration range studied while the binding to alpha1-AGP decreased with increasing drug concentration indicating that albumin is more important in clinical settings.
alpha1-AGP might be important when plasma proteins change with disease. The results to plasma obtained by CPE were in good agreement to those observed by ultrafiltration and equilibrium dialysis, indicating that CPE was a highly sensitive and selective method for the measurement to plasma protein binding of TSG. The results obtained in our studies are important before clinical trials and to perform pharmacokinetic studies.
我们通过三种不同方法（超滤、平衡透析和浊点萃取）研究了芪苷（2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷，TSG）与血浆、白蛋白和α1-AGP（2.0、10.0 或 50μg/mL）的结合情况，这是一项前瞻性研究。
在不同温度（4、25 和 37°C）以及解冻和冷冻条件下评估了血浆中药物的稳定性。采用经过验证的高效液相色谱（HPLC）方法分析了样品中总药物浓度和游离分数。
TSG 与血浆的结合随药物浓度的增加而增加。与白蛋白的结合在研究浓度范围内保持恒定（约 60%），而与α1-AGP 的结合随药物浓度的增加而降低，这表明白蛋白在临床环境中更为重要。
当血浆蛋白因疾病而发生变化时，α1-AGP 可能很重要。浊点萃取法（CPE）得到的血浆结果与超滤和平衡透析观察到的结果非常吻合，这表明 CPE 是一种高度灵敏和选择性的 TSG 与血浆蛋白结合测量方法。在临床试验和进行药代动力学研究之前，这些研究结果非常重要。
