The effect of stationary phase on lipophilicity determination ofβ-blockers using reverse-phase chromatographic systems

Abstract

Evaluation of lipophilicity parameters for basic compounds using different chromatographic stationary phases is presented. An HPLC method for determination of lipophilic molecule-stationary phase interactions was based on gradient analysis. Differences in correlation between the lipophilicity of compounds and experimental chromatographic results obtained in pseudo-membrane systems showed a strong influence of stationary phase structure and physico-chemical properties. beta-Blocker drugs with varying lipophilicity and bio-activity were chosen as test compounds. The stationary phases used for the study were monolithic rod-structure C18 and silica gel octadecyl phase SG-C18 as reference material. The second group was silica gel-based polar-embedded alkylamide and cholesterolic phases. The mobile phase was composed of acetonitrile or methanol with ammonium acetate, and a linear gradient of methanol and acetonitrile in mobile phase was performed. A linear correlation of plots of log k(g) = f(log P) was observed, especially for polar-embedded phases, and this allowed log P(HPLC) to be calculated. The behavior of stationary phases in methanol and acetonitrile buffer showed differences between obtained log P(HPLC) values.

Analytical tools for the physicochemical profiling of drug candidates to predict absorption/distribution

“…An alternative strategy which does not require complex calculation procedure involves assuming that S is constant for structurally similar compounds. Although this approach is evidently less accurate than the former, it allows estimation log k w from a single gradient run [92,[178][179][180][181][182]. Based on this assumption, Valko and coworkers introduced the chromatographic hydrophobicity index (CHI), derived from the ϕ 0 scale [183][184][185][186][187][188].…”

“…Using such columns, there is no need to add a masking agent such as triethylamine and n-decylamine because of the lower amount of free silanols. Finally, monolithic silica stationary phases were also tested for fast lipophilicity determination, but their use remains limited [182].…”

Cholesterol-based polymeric monolithic columns for capillary liquid chromatography

“…The most important advantage of the cholesterol stationary phase is that it can be successfully used in both normal-and reversed-phase liquid chromatography. The compounds resolved include, e.g., antibiotics [5], benzodiazepines [6], flavonoids [7], polycyclic aromatic hydrocarbons (PAHs) [1,[8][9][10], steroids [11][12][13], beta-blockers [14,15] and different xenobiotics [4]. Additionally, commercially available cholesterol-based chromatographic columns (Cosmosil Cholester and Cogent TM UDC-cholesterol) were used in other applications, e.g., separation of catechins, saikosaponins, carotenes, vitamin K isomers [16,17].…”

Determination of lipophilicity of novel potential antituberculotic agents using HPLC on monolithic stationary phase and theoretical calculations

“…Unfortunately, shake-flask method is extremely time-consuming and laborintensive, it requires a high purity of tested substances and often suffers from solubility and stability problems. Hence, nowadays this complicated approach was nearly completely substituted by modern chromatographic techniques [6][7][8][9][10][11][12]. Among them, HPLC is the leading and the most frequently used chromatographic method for the routine lipophilicity determination, since it enables rapid, accurate and highly reproducibility analysis of relatively large sets of samples.…”