摘要
建立快速微乳液相色谱法(MELC)测定药物的油-水分配系数(log P)的方法.选择5种模拟生物膜的微乳流动相体系,以7个标准药物的log P对保留因子(log k)的回归线性方程,计算被测药物的log P值.并以药物文献的log P值对实验测得log k值的线性相关系数为参数,对微乳体系的表面活性剂和油相的种类进行考察,得到测定非同类的中性、碱性药物的油-水分配系数最佳流动相体系为6.0%Brij35-6.6%正丁醇-0.8%正辛醇-86.6%磷酸缓冲液(0.05 mol·L-1,pH 7.0),其测得值与文献的实验值平均相差0.3个对数单位.结果显示该方法可靠、高效、重现性好,可用于药物的油-水分配系数log P的测定.
A rapid screening assay determination of octanol-water partition coefficients （log P） of pharmaceuticals was developed by using microemulsion liquid chromatography （MELC）. Seven standard compounds with known log P values were used for constructing the calibration curve of log P against the MELC log k, by which the log P values of the pharmaceuticals were calculated. The types of surfactants and oil phase were evaluated in the microemulsion systems using such parameters as linear correlation coefficients the literature log P values against the experimentally measured log k values. The optimized MELC system with microemulsion consisting of 6.0% polyoxyethylene lauryl ether （Brij35）-6.6% butanol-0.8% octanol-86.6% phosphate buffer （0.05 mol·L^-2, pH 7.0） shows good correlation （r=0.96） to the experimental log P （Elog P） values for noncongeneric neutral and basic pharmaceuticals. The average error of log P values measured by MELC is within 0.3 log unit of the values from the literature. The results indicate that MELC can serve as a high throughput, reliable and robust approach and as a valid model for log P determinations.
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2009年第18期2116-2120,共5页
Acta Chimica Sinica
关键词
微乳液相色谱
油-水分配系数
LOG
P
microemulsion liquid chromatography
oil-water partition coefficient
log P
