Lipophilicity Determination of Highly Lipophilic Compounds by Liquid Chromatography

Abstract

Different experimental strategies using short columns in both conventional liquid chromatography (HPLC) and ultra-high pressure liquid chromatography (UHPLC) were evaluated to allow, for the first time with these techniques, the lipophilicity determination of compounds with log P>5. Various organic modifiers, stationary phases, and elution modes were tested on 14 rigid compounds with a CLogP between 5 and 8, and 38 compounds with log P(oct) from 0 to 5. The best results in HPLC were obtained with the 20-mm Discovery RP Amide C16 stationary phase in isocratic mode using MeOH as organic modifier. To improve analysis time, the UHPLC approach was then evaluated. Consequently, a generic method was developed with a 30-mm Acquity BEH Shield RP18 column in gradient mode using MeOH as organic modifier, allowing a fourfold gain of time compared to the HPLC method, for the highly lipophilic compounds tested. Finally, the most rapid and accurate results were obtained with a 10-mm Hypersil GOLD Javelin HTS stationary phase in UHPLC, enabling an eightfold gain of time compared to the HPLC method.

Reversed-Phase TLC and HPLC Retention Data in Correlation Studies with in Silico Molecular Descriptors and Druglikeness Properties of Newly Synthesized Anticonvulsant Succinimide Derivatives

“…The mixture was heated at 70°C for 2 h. Acetic anhydride was removed under vacuum, and the crude material was purified by crystallization. The chemical structures and the purities of the synthesized succinimides were confirmed by melting points and the 1 H NMR, 13 C NMR, FT-IR and UV spectra.…”

“…That is as expected because the empirical chromatographic lipophilicity parameters are known to agree with the log P values. 6,9,13 However, such a correlation needs an empirical verification for individual sets of congeners.…”

B3LYP Study of 3-hydroxynaphthalene-2-carboxanilide para-derivatives

“…All these properties strongly depend on the lipophilicity of the compound making it one of the key parameters in the prediction and determination of pharmacological activity of potential drugs. [12][13][14][15] Lipophilicity as defined by IUPAC is the affinity of a molecule or its moiety to lipophilic environment. 16 Generally, it is expressed as octanol-water partition coefficient P, which can be determined experimentally and by computational methods.…”

The study of retention regularities for the potential drug substances of 1,2,4-triazol-3-ylthioacetic acids and their salts series by the method of HPLC/DAD-MS

“…де P ij -коефіцієнт розподілу речовин між фазами i та j. Ряд публікацій присвячений дослідженню взаємозв'язку між характеристиками утримування та коефіцієнтами розподілу, які найчастіше використовуються для визначення характеристик ліпофільності за результатами утримування в обернено-фазовій ВЕРХ (ОФ ВЕРХ) [2][3][4][5][6][7][8][9]. Авторами [10] наведені дані щодо визначення ліпофільності нових тіосемікарбазидів та похідних 1,2,4-триазол-3-тіонів на підставі результатів ОФ ВЕРХ та теоретичних розрахунків.…”