Chromatographic Approaches for Measuring Log P

Abstract

AbbreviationsADMET absorption, distribution, metabolism, elimination and toxicity CE capillary electrophoresis CHI chromatographic hydrophobicity index IAM immobilized artifi cial membrane LC liguid chromatography LEKC/VEKC liposome/vesicular electrokinetic chromatography LSER linear solvation energy relationship LSS linear solvent strength MEEKC microemulsion electrokinetic chromatography MEKC micellar electrokinetic chromatography MS mass spectrometry ODP octadecyl polyvinyl ODS octadecylsilane OS octylsilane PC phosphatidylcholine QSAR quantitative structure -activity relationship RPLC reversed -phase liquid chromatography SDS sodium dodecyl sulfate UV ultraviolet Symbols S slope V D system dwell volume log P oct octanol -water partition coeffi cient 331 Molecular Drug Properties. Measurement and Prediction. R. Mannhold (Ed.)

Lipophilicity Determination of Highly Lipophilic Compounds by Liquid Chromatography

“…-Thirty-eight analytes with log P oct values ranging from 0 to 5 were selected by cluster analysis to obtain a well-balanced set of compounds in terms of molecular chemical properties [10]. Based on their calculated CLogP values (between 5 and 8), 14 rigid compounds were chosen to avoid problems related to the neglect of molecular 3D-structure effects in lipophilicity prediction [3]. The log k w values of the 52 compounds were determined under their neutral form with three different stationary phases (Discovery RP Amide C16 with HPLC system, and Acquity BEH Shield RP18 and Hypersil TM GOLD Javelin HTS with UHPLC system), and different experimental conditions were evaluated with each column: i) isocratic mode with MeOH as organic modifier, ii) gradient mode with MeOH, and iii) isocratic mode with MeCN.…”

Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA)

“…Clear differences in passive permeability could be evidenced for the different constituents of the extracts. Such dissimilarities between these profiled metabolites could not simply be based on their polarity (such as their retention times [50,51]). These findings have also indicated that the presence of multiple component mixtures did not influence the passive permeability of single constituents and thus that the passive absorption of NPs seemed not to be potentially influenced by synergistic aspects in the frame of the HDM-PAMPA predictions.…”

High‐throughput log P determination by MEEKC coupled with UV and MS detections

“…This issue can be solved (i) by adding 1-octanol to the mobile phase, which acts as a weak masking agent reducing secondary interactions due to residual silanol groups but with long equilibration times [20,21] Electrophoresis 2010, 31, 952-964 952 by using isocratic log k values measured at 50% methanol [17,18]. In this context, CE is emerging as an attractive technique for log P determination thanks to numerous advantages: (i) small solvent and sample consumption, (ii) highly pure samples not needed, (iii) automation, and (iv) low cost [13][14][15][22][23][24][25][26].For lipophilicty determination by CE, it is necessary to work with a BGE allowing the separation of neutral compounds. Different CE modes have been tested, namely MEKC, MEEKC, and LEKC/VEKC (micellar, microemulsion (ME) and liposome/vesicle EKC, respectively).…”

“…However, this technique is only appropriate for ionizable compounds and requires milligram amounts of pure sample. The LC approach is a good alternative as it presents some inherent advantages: (i) small sample consumption, (ii) highly pure samples not required due to its separation power, (iii) automation, and (iv) wide range of measurable log P oct values (from À1 to 8) [11,[13][14][15][16]. Furthermore, HTS methods have been reported thanks to the recent development of ultra high pressure liquid chromatography (UHPLC) [17,18].…”