Lipophilicity assessment of basic drugs (logPo/w determination) by a chromatographic method

Pallicer, Juan M.; Sales, Joaquim; Rosés, Martı́; Ràfols, Clara; Bosch, Elisabeth

doi:10.1016/j.chroma.2011.07.002

Cited by 28 publications

(15 citation statements)

References 35 publications

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“…More recently, a study used CNS drugs and tested them in a mouse model where genes that encode the P-gp efflux pumps have been knocked out. This study demonstrated that out of 34 CNS drugs, only 7 showed no evidence of efflux using -1 to 5.9 --PSA-dependent [55] Bioavailability ---2 to 3 [56] 0 to 3 -- [42] --1 to 3 [58] < 3 --Ionization-dependent [11] Distribution " better --Ionization-dependent [11] CNS Penetration " better --MW-dependent [11,71] > 2 --…”

Section: Cns Penetrationmentioning

confidence: 90%

“…The chromatographic hydrophobicity index (CHI) developed by Valko et al can be used as an independent measure of hydrophobicity [44] and offers a simple way to evaluate the log P of a drug [45]. In fact, the need to correct chromatographic measurements with the hydrogen bond acidity to get reliable log P values has been demonstrated recently [42,46]. This is a remarkable feature since pure chromatographic methods only offer good estimations of log P for compounds without significant hydrogen bond acidity.…”

Section: Measuring Lipophilicitymentioning

confidence: 97%

“…These include attempts to automate the traditional shake-flask method to a 96-well format and [40], chromatographic methods such as reversed-phase (RP)-HPLC, electrophoretic methods such as microemulsion electrokinetic chromatography (MEEKC), and immobilized artificial membrane (IAM) HPLC-columns (for a review see [3,41,42]). Among the chromatographic methods, RP-HPLC has been at the forefront of lipophilicity determination and is the method of choice for many laboratories.…”

Section: Measuring Lipophilicitymentioning

confidence: 99%

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The influence of lipophilicity in drug discovery and design

Arnott

Planey

2012

Expert Opinion on Drug Discovery

603

455

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A current review of the literature reveals a continued reliance on the synthesis of novel structures with increased potency, rather than a focus on maintaining optimal physicochemical properties associated with ADMET throughout drug optimization. Particular attention to the optimum region of lipophilicity, as well as monitoring of lipophilic efficiency indices, may contribute significantly to the overall quality of candidate drugs at different stages of discovery.

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Section: Cns Penetrationmentioning

confidence: 90%

Section: Measuring Lipophilicitymentioning

confidence: 97%

Section: Measuring Lipophilicitymentioning

confidence: 99%

See 1 more Smart Citation

The influence of lipophilicity in drug discovery and design

Arnott

Planey

2012

Expert Opinion on Drug Discovery

603

455

View full text Add to dashboard Cite

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“…On the other hand, the negative sign of the coefficient at the analyte polarity descriptor l 2 proves stronger attractions between the analyte and the polar eluent molecules than between the same analyte molecule and the nonpolar hydrocarbon ligand of the stationary phase. [1,14] The value (negative) of the coefficient k 2 at dipole moment square in Table 6, regarding the methanol-modified systems, is largest for the Unison UK-C18 column and smallest for the Zorbax SB-C18 column. In the case of acetonitrile as the organic modifier, the largest is the respective coefficient (negative) for the MICRA NPS ODS I column and Unison UK-C18 column and the smallest for the Zorbax SB-C18 column.…”

Section: Resultsmentioning

confidence: 96%

Thermodynamic and QSRR Modeling of HPLC Retention on Modern Stationary Phases

Kaczmarek

Buciński

Marszałł

et al. 2014

Journal of Liquid Chromatography & Related Technologies

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This paper investigates correlations between the standard chromatographic parameter, log k w , obtained experimentally (classical thermodynamic) and obtained through the use of quantitative structure-retention relationships (QSRR) models (extrathermodynamic approach). QSRR models were created using descriptors from calculation chemistry, selected a priori on the basis of chemical intuition. Four modern analytical columns (packed with C18), often used in pharmaceutical analysis, were selected for the study. The simple extrathermodynamic model was demonstrated to be superior in terms of retention description with relation to rather complex models based on thermodynamic hermeneutics. However, all the QSRR equations derived are of limited predictive value as regards prediction of retention on the basis of the structure of the analyte. Nonetheless, they allow the differentiation of mechanism of separation operating on individual tested stationary phases. The descriptors, which are most significant in QSRR equations, appear to characterize better the net effect of interactions of the analytes with the stationary phases and the mobile phase containing acetonitrile as compared to the HPLC systems comprising methanol. These observations suggest that retention properties of new stationary phases studied in this work differ.

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“…The analysis of the dis- 46 solution mechanisms and the prediction of API dissolution profiles 47 from intrinsic dissolution as well as from actual tablets are chal- 48 lenging topics in pharmaceutical development. In the last decades, 49 several empirical, semi-empirical and mechanistic mathematical 50 models have been proposed to describe the API dissolution profiles 51 from a variety of solid pharmaceutical dosage forms, e.g. matrix 52 systems [1][2][3], erodible tablets [4,5], microspheres [6], hydrogels 53 [7], powders [8] and immediate release tablets [9][10][11][12].…”

mentioning

confidence: 99%