Jia Zhongjiang, Mei Lijie, Lin Fangling, Huang Sujuan, Killion Robert B
Department of Pharmaceutics, Roche Palo Alto LLC, 3431 Hillview Avenue, R1-3 Palo Alto, CA 94304, USA.
J Chromatogr A. 2003 Jul 25;1007(1-2):203-8. doi: 10.1016/s0021-9673(03)00949-x.
A rapid screening assay for the determination of octanol-water partition coefficients (log P(OW)) of pharmaceuticals was developed by using pressure-assisted microemulsion electrokinetic chromatography (MEEKC). The microemulsion system contains 50 mM sodium dodecyl sulfate, 0.87 M l-butanol, 82 mM heptane, and 50 mM borate-phosphate (2:3) at pH 10. Ten standard compounds with known log P(OW) values from -0.26 to 4.88 were used for constructing the calibration curve of log P(OW) against the MEEKC retention factor, log k. The log P(OW) values of the compounds were calculated based on the log k values measured by MEEKC and the slope and intercept of the calibration curve. For 13 literature and 32 Roche compounds, about 90% of the log P(OW) values measured by MEEKC are within 0.5 log units of the values from the literature and potentiometric titration. The throughput is about 2 samples/h using +20 kV voltage plus 5 mbar air pressure for separation. This MEEKC method is applicable for log P(OW) screening of weakly basic, weakly acidic, and neutral pharmaceuticals with log P(OW) = 0-5 and pKa < or = 10.
采用压力辅助微乳液电动色谱法（MEEKC）开发了一种快速筛选方法，用于测定药物的正辛醇-水分配系数（log P(OW)）。该微乳液体系含有50 mM十二烷基硫酸钠、0.87 M正丁醇、82 mM庚烷和50 mM硼酸盐-磷酸盐（2:3），pH为10。使用10种log P(OW)值已知在-0.26至4.88之间的标准化合物构建log P(OW)与MEEKC保留因子log k的校准曲线。根据MEEKC测得的log k值以及校准曲线的斜率和截距计算化合物的log P(OW)值。对于13种文献报道的化合物和32种罗氏化合物，通过MEEKC测得的log P(OW)值约90%在文献报道值和电位滴定值的0.5个log单位范围内。使用+20 kV电压加5 mbar气压进行分离时，通量约为2个样品/小时。这种MEEKC方法适用于log P(OW) = 0 - 5且pKa≤10的弱碱性、弱酸性和中性药物的log P(OW)筛选。
