Analysis of anticancer platinum(II)-complexes by microemulsion electrokinetic chromatography: Separation of diastereomers and estimation of octanol-water partition coefficients
Analysis of anticancer platinum(II)-complexes by microemulsion electrokinetic chromatography: Separation of diastereomers and estimation of octanol-water partition coefficients
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DOI：
10.1002/elps.200410053
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发表时间：
2005-02-01
期刊：
影响因子：
2.9
通讯作者：
Keppler, BK
中科院分区：
文献类型：
--
作者：
Rappel, C;Galanski, M;Keppler, BK
采用微乳电动色谱法（MEEKC）对奥沙利铂及8种新型抗癌奥沙利铂衍生物进行分离和亲脂性评价。在现代药物开发中，溶解度和渗透性必须得到平衡，辛醇-水分配系数（log P）仍然是提供药物亲脂性合理估计的最有用的可量化参数之一。因此，MEEKC的容量因子与传统摇瓶法得到的对数P值相关。IVIEEKC方法在pH 7.4和37℃的磷酸盐缓冲液中使用庚烷/十二烷基硫酸钠(SDS)/丁醇微乳液完成，所有分析物在运行过程中处于中性状态。该实验装置允许在11分钟内对所有铂配合物进行基线分离。值得注意的是，除了非常好的分辨率和测量精度外，还可以实现配合物的非对映体分离和非对映体比例的定量。将容量因子与相应的对数P值相关联，产生线性相关性，相关因子r = 0.9935。因此，与其他方法相比，应用IVIEEKC方法不仅对铂配合物的分离有很高的价值，而且对辛醇-水分配系数的估计也有许多优点。
Microemulsion electrokinetic chromatography (MEEKC) was applied for the separation and lipophilicity estimation of oxaliplatin and eight novel anticancer oxaliplatin derivatives. Solubility and permeability have to be balanced in modern drug development, and the octanol-water partition coefficient (log P) still represents one of the most useful quantifiable parameters providing a reasonable estimation of a drug's lipophilicity. Therefore, the capacity factors from MEEKC were correlated to log P values derived by the traditional shake flask method. The IVIEEKC method was accomplished using a microemulsion of heptane/sodium dodecyl sulfate (SDS)/butanol in phosphate buffer at pH 7.4 and 37degreesC with all analytes being in a neutral state during the run. This experimental setup allowed a baseline separation of all platinum complexes within 11 min. Remarkably, beside the very good resolution and precision of the measurements, separation of diastereomers of the complexes and quantification of the diastereomeric ratios could be achieved. Correlating the capacity factors with the corresponding log P values resulted in a linear dependency with a correlation factor of r = 0.9935. Consequently, the applied IVIEEKC method was found to be a highly valuable technique not only for the separation of platinum complexes but as well for the estimation of the octanol-water partition coefficient with many advantages in comparison to other methods.