Estimation of the Partitioning Characteristics of Drugs:  A Comparison of a Large and Diverse Drug Series Utilizing Chromatographic and Electrophoretic Methodology

Abstract

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.

Biomembrane lipids as components of chromatographic phases: Comparative chromatography on coated and bonded phases

“…Following recycling of an aqueous-methanolic solution of soybean lecithin phosphatidylcholine (SLPC) (1 mM), through a C8 stationary phase for 18 hours, the quantity of lipid coated on to the phase was estimated to be approximately 35 mg by UV analysis of the coating solution both prior to and post coating [28]. The chromatographic properties of the coated phase were then evaluated by examination of the retention characteristics of a range of compounds, including acidic, basic and neutral analytes, selected from the compound library (Table I).…”

“…We have adopted an alternative approach to the application of biomembrane lipids as components of chromatographic stationary phases [28]. A phase prepared by dynamically coating soybean lecithin phosphatidylcholine onto a reversedphase (C8) column was used for the prediction of log P octanol/water data of a large and structurally diverse compound library comprising acids, bases and neutral compounds, with a variety of pharmacological activities and physicochemical properties (e. g. log P range 0.52 to 7.63).…”

Analysis of sulfonamides by capillary electrophoresis

“…Another method using MEKC analysis was published in 1998 [49]. The authors aimed to obtain log P values for a very large series of drugs, including SFAs.…”

Comparison of C18 silica bonded phases selectivity in micellar liquid chromatography

“…Cline Love and Fett [36] used for the column void volume determination distilled water, and measuring the time of the first deviation from the baseline. Hanna et al [37] used the same method for the dead time (volume) determination.…”