Database of published retention factors for immobilized artificial membrane HPLC and an assessment of the effect of experimental variability

Abstract

A database was collated of published experimental logarithmic values for the relative retention factors (log k(IAM)) measured using an immobilized artificial membrane column and high-performance liquid chromatography (IAM HPLC). Log k(IAM) is an alternative measure of hydrophobicity to the octanol/water partition coefficient (log K(OW)). While there are several accepted methods to measure log K(OW), no standardized method exists to determine log k(IAM). The database of collated log k(IAM) values includes 13 key experimental parameters and contains 1,686 values for 555 compounds, which are predominantly polar organic compounds and include drug molecules and surfactants. These compounds are acidic, basic, and neutral and both ionized and un-ionized under the conditions of analysis. The data compiled demonstrated experimental variability for each experimental parameter considered, including column stationary phase, pH, temperature, and mobile phase. Reducing the experimental variability allowed for greater consistency in the datasets.

Dealing with Confounding pH-Dependent Surface Charges in Immobilized Artificial Membrane HPLC Columns

“…IAM-HPLC data are regularly published for many ionizable pharmaceuticals (e.g., see refs − ). The simplicity and consistency of a chromatographic tool seems ideal to create a vast, high quality data set of K PLIPW,ion values . These IAM-retention values for ionizable chemicals, however, were not considered by the aforementioned reviews on K PLIPW,ion values, − because of concerns raised in several IAM-HPLC studies on confounding charged groups on IAM particles.…”

“…The simplicity and consistency of a chromatographic tool seems ideal to create a vast, high quality data set of K PLIPW,ion values. 28 These IAMretention values for ionizable chemicals, however, were not considered by the aforementioned reviews on K PLIPW,ion values, 8−10 because of concerns raised in several IAM-HPLC studies on confounding charged groups on IAM particles. The charged groups influence the retention capacity factors of strongly ionized compounds.…”

Sorption of Cationic Surfactants to Artificial Cell Membranes: Comparing Phospholipid Bilayers with Monolayer Coatings and Molecular Simulations

“…23 Recently, immobilized artificial membrane HPLC columns (IAM-HPLC) have been used to determine (relative) measures of lipophilicity in a number of frameworks. 24−27 Confounding pH-dependent surface charges in IAM-HPLC have recently been recorded in detail. 28 These surface charges can considerably influence the retention capacity factors of IOCs on IAM-HPLC physiological pH.…”

“…Methods employing dispersions of freshly prepared liposomes are most realistic and accurate, but equilibrium dialysis requires considerable effort and long equilibration times. , Potentiometric titrations need substantial concentrations of chemical and phospholipids . Recently, immobilized artificial membrane HPLC columns (IAM-HPLC) have been used to determine (relative) measures of lipophilicity in a number of frameworks. − Confounding pH-dependent surface charges in IAM-HPLC have recently been recorded in detail . These surface charges can considerably influence the retention capacity factors of IOCs on IAM-HPLC physiological pH. − At least for cationic compounds, confounding surface charges can be avoided by testing at low pH and highly saline eluent medium, and therewith one can specifically determine the IAM phospholipid–water distribution coefficient for the ionic form ( K IAM,ion ) .…”

Robustness of an Immobilized Artificial Membrane High-Performance Liquid Chromatography Method for the Determination of Lipophilicity

“…Ledbetter et al 12 optimized an IAM-HPLC method to determine the logarithm of the IAM-HPLC retention index (log k IAM (pH 7.4) ); the method was used to determine log k IAM (pH 7.4) for 66 compounds covering highly hydrophilic and highly hydrophobic compounds (log K OW = −1.35 to 6.03), as well as compounds ionized under the conditions of analysis. A good correlation was obtained between log K OW and log k IAM (pH 7.4) (n = 66, r 2 adj = 0.865, s = 0.561, F = 418) 13 (full data is available as Supporting Information, SI, Tables 1 and 2).…”