Domenici E, Bertucci C, Salvadori P, Motellier S, Wainer I W
Dipartimento di Chimica e Chimica Industriale, Universita di Pisa, Italy.
Chirality. 1990;2(4):263-8. doi: 10.1002/chir.530020412.
A human serum albumin-based HPLC chiral stationary phase (HSA-CSP) has been examined as a tool to investigate binding of chiral drugs to HSA and drug-drug protein-binding interactions. Rac-oxazepam hemisuccinate (OXH) was used as a model compound and the chromatographic retention (k') of its enantiomers was determined after addition of displacers to the mobile phase. Compounds known to bind at the same site as OXH and at different sites were tested for their displacing capacities. Competitive binding interactions between the OXH enantiomers and displacers in the mobile phase were reflected by decreases in the k's of (R)- and (S)-OXH. The results indicate that retention on the HSA-CSP accurately reflects binding to native HSA and the technique can determine enantioselective and competitive binding interactions at specific sites on HSA. The HSA-CSP was also able to recognize separate binding areas for (S)- and (R)-OXH.
一种基于人血清白蛋白的高效液相色谱手性固定相（HSA-CSP）已被作为一种工具来研究手性药物与HSA的结合以及药物-药物蛋白结合相互作用。消旋奥沙西泮半琥珀酸酯（OXH）被用作模型化合物，在向流动相中加入置换剂后测定其对映体的色谱保留值（k'）。测试了已知在与OXH相同位点和不同位点结合的化合物的置换能力。流动相中OXH对映体与置换剂之间的竞争性结合相互作用通过（R）-和（S）-OXH的k'值降低来反映。结果表明，在HSA-CSP上的保留准确反映了与天然HSA的结合，该技术可以确定HSA上特定位点的对映选择性和竞争性结合相互作用。HSA-CSP还能够识别（S）-和（R）-OXH的不同结合区域。
