Reversed-phase high-performance liquid chromatography for evaluating the lipophilicity of pharmaceutical substances with ionization up to log Papp = 8

Belsner, Klaus; Pfeifer, Martina; Wilffert, Bob

doi:10.1016/0021-9673(93)87027-j

Cited by 33 publications

(14 citation statements)

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“…Distribution of the investigated compounds in the parameter space of the Van der Waals volume V w , dipolarity/polarizability p*, H-bond acceptor basicity b and the H-bond donor acidity a probably due to the lower quality of the linear regression between log k vs. f. After omission of the two outliers, the correlation between log k w and S becomes excellent (r 2 0.99). In previous studies, good correlations between log k w and S were obtained only for simple or closely related compounds [13] [16] [17]. Here, significant correlations were obtained for a structurally diverse set of analytes including model compounds and drugs.…”

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confidence: 87%

Lipophilicity Measurement by Reversed‐Phase High‐Performance Liquid Chromatography (RP‐HPLC): A Comparison of Two Stationary Phases Based on Retention Mechanisms

Liu

Tanaka

Yamauchi

et al. 2004

Helvetica Chimica Acta

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The mechanisms of retention of two recent stationary phases of interest in lipophilicity measurements, namely of the silica-based Discovery-RP-Amide-C16 phase and the polymer-based ODP-50-4B phase, were assessed and compared. A set of 41 model solutes and drugs with well-defined solvatochromic parameters were selected to allow a broad distribution of property spaces. The chromatographic results showed that, under the conditions of study, the lipophilicity index log k w obtained with the former stationary phase was more closely related to experimental log P oct values than was log k w obtained with the ODP-50-4B phase. Linear solvation/ free-energy relationship (LSER) analyses showed that the retention mechanisms of the two stationary phases are different, retention on the Discovery-RP-Amide-C16 phase and partitioning in octan-1-ol/H 2 O being controlled by the same balance of intermolecular forces (Van der Waals volume V w , H-bond acceptor basicity b, and dipolarity/polarizability p*).Introduction. ± The lipophilicity of solutes, traditionally expressed by their partition coefficients in the octan-1-ol/H 2 O system (noted log P oct ), is of high significance from both a physicochemical and a pharmacological viewpoint [1] [2]. The partitioning process expresses the combined effects of a number of intermolecular forces between a solute and its environment, here the solvents between which the solute partitions. These intermolecular forces are of particular importance in pharmacology since they also control the partitioning of solutes into biomembranes. Numerous studies have reported a relationship between log P oct and absorption or permeability in cell cultures and tissue preparations used as models of, e.g., the gastrointestinal tract or the bloodbrain barrier [3 ± 7].The reference procedure to measure log P oct is the shake-flask method which, however, is time-consuming and limited in range (ca. À 3 < log P < 4). Beyond these limits, log P oct values measured by the shake-flask method become unreliable.The reversed-phase HPLC method is a promising alternative to the shake-flask method, having such advantages as a higher throughput, an insensitivity to impurities or degradation products, and a broader lipophilicity range. In reversed-phase HPLC, lipophilicity indices are derived from the capacity factor log k, which is calculated by Eqn. 1, where t R and t 0 are the retention times of the solute and of an unretained compound, respectively. Some workers have used isocratic log k values measured in an appropriate mobile phase as a lipophilicity parameter [8 ± 10]. However, many more investigators use capacity factors extrapolated to 100% H 2 O (log k w ) to eliminate organic-solvent effects [11 ± 15], and they have indeed demonstrated the usefulness of

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confidence: 87%

Lipophilicity Measurement by Reversed‐Phase High‐Performance Liquid Chromatography (RP‐HPLC): A Comparison of Two Stationary Phases Based on Retention Mechanisms

Liu

Tanaka

Yamauchi

et al. 2004

Helvetica Chimica Acta

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“…The use of reversed-phase liquid chromatography for the indirect determination of octanol-water partition coefficients was proposed in the early 1970s and has been reviewed many times since [7][8][9]11,16,17,[45][46][47][48][49]. In spite of many attempts, success has been limited for compounds that exhibit structural diversity.…”

Section: Reversed-phase Liquid Chromatographymentioning

confidence: 99%

Separation methods for estimating octanol–water partition coefficients

Poole

2003

Journal of Chromatography B

220

154

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“…Consequently, the primary aim of the present study was to examine the impact of the mass of co‐administered lipid on the in vitro digestion behaviour and the oral bioavailability of a model lipophilic poorly water‐soluble drug (CZ) after administration of simple triacylglyceride solution formulations. CZ (log p = 5.77)21 was selected as the model poorly water‐soluble drug because the oral bioavailability of CZ is limited by solubilisation and dissolution, and hence CZ is a Class 2 compound according to the Biopharmaceutical Classification System 22…”

Section: Introductionmentioning

confidence: 99%

The Effect of Administered Dose of Lipid-Based Formulations on the In Vitro and In Vivo Performance of Cinnarizine as a Model Poorly Water-Soluble Drug

Lee

Porter

Boyd

2013

Journal of Pharmaceutical Sciences

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Reversed-phase high-performance liquid chromatography for evaluating the lipophilicity of pharmaceutical substances with ionization up to log Papp = 8

Cited by 33 publications

References 8 publications

Lipophilicity Measurement by Reversed‐Phase High‐Performance Liquid Chromatography (RP‐HPLC): A Comparison of Two Stationary Phases Based on Retention Mechanisms

Lipophilicity Measurement by Reversed‐Phase High‐Performance Liquid Chromatography (RP‐HPLC): A Comparison of Two Stationary Phases Based on Retention Mechanisms

Separation methods for estimating octanol–water partition coefficients

The Effect of Administered Dose of Lipid-Based Formulations on the In Vitro and In Vivo Performance of Cinnarizine as a Model Poorly Water-Soluble Drug

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