Estimation of the partitioning characteristics of drugs: A comparison of a large and diverse drug series utilizing chromatographic and electrophoretic methodology

被引:64
作者
Hanna, M
de Biasi, V
Bond, B
Salter, C
Hutt, AJ
Camilleri, P
机构
[1] SmithKline Beecham Pharmaceut, Dept Pharm, Harlow CM19 5AW, Essex, England
[2] Kings Coll London, Dept Pharm, London SW3 6LX, England
关键词
D O I
10.1021/ac971122l
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
1-Octanol-water log P values for a large number of standards and bioactive molecules have been correlated to the logarithm of the corresponding capacity factors determined by reversed-phase high-performance liquid chromatography, using a novel dynamically coated phase, containing phosphatidylcholine. Similarly a correlation was also obtained for log P and capacity factors determined by micellar electrokinetic capillary chromatography (MECC), involving the use of phosphatidylcholine - bile acid mixed micelles in the separation buffer. Statistical analysis of data obtained via both methods has shown that either method will give reliable log P predictions, although MECC is generally more useful for neutral and basic compounds. It is recommended that, as both methods can easily be set up in an analytical laboratory, their combined use provides rapid methodology for the confident estimation of hydrophobicity, as measured by log P for the widest diversity of chemical structures.
引用
收藏
页码:2092 / 2099
页数:8
相关论文
共 18 条
[1]   RAPID ESTIMATION OF OCTANOL-WATER PARTITION-COEFFICIENTS USING DEOXYCHOLATE MICELLES IN CAPILLARY ELECTROPHORESIS [J].
ADLARD, M ;
OKAFO, G ;
MEENAN, E ;
CAMILLERI, P .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1995, (21) :2241-2243
[2]   PARTITIONING OF IONIZING MOLECULES BETWEEN AQUEOUS BUFFERS AND PHOSPHOLIPID-VESICLES [J].
AUSTIN, RP ;
DAVIS, AM ;
MANNERS, CN .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1995, 84 (10) :1180-1183
[3]   Interactions of nonsteroidal antiinflammatory drugs with phospholipids: Comparison between octanol/buffer partition coefficients and chromatographic indexes on immobilized artificial membranes [J].
Barbato, F ;
LaRotonda, MI ;
Quaglia, F .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1997, 86 (02) :225-229
[5]   DETECTION OF INFLUENTIAL OBSERVATION IN LINEAR-REGRESSION [J].
COOK, RD .
TECHNOMETRICS, 1977, 19 (01) :15-18
[6]   INFLUENTIAL OBSERVATIONS IN LINEAR-REGRESSION [J].
COOK, RD .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1979, 74 (365) :169-174
[7]  
Craig P, 1990, CUMULATIVE SUBJECT I, P237
[8]  
DRAPER NR, 1981, APPL REGRESSION ANAL, P69
[9]  
Hansch C., 1979, Substituent constants for correlation analysis in chemistry and biology
[10]   N-OCTANOL WATER PARTITION-COEFFICIENT ESTIMATION BY MICELLAR ELECTROKINETIC CAPILLARY CHROMATOGRAPHY [J].
HERBERT, BJ ;
DORSEY, JG .
ANALYTICAL CHEMISTRY, 1995, 67 (04) :744-749