Lipophilicity measurement

Several approaches for higher throughput lipophilicity measurements have been developed in the pharmaceuhcal industry [50] including automated shake-plate methods [84] and immobilized arhficial membranes [85]. A convenient method to... 

Due to instrumental or laboratory variability, the information given by the experimental gradient retention times (tr) is not sufficient to obtain accurate and repeat-able logP values [38]. As described by Eqs. (4), (6) and (7) the lipophilicity measurement in gradient mode is therefore based on the determination of logfeo and S because both terms are necessary to obtain log few. 

Gocan, S., Gimpan, G., Comer, J. Lipophilicity measurements by liquid chromatography. Adv. Chromatogr. 2006, 44, 79-176. 

Stella, C., Galland, A., liu, X., Testa, B., Rudaz, S., Veuthey, J. L, Carrupt, P. A. Novel RPLC stationary phases for lipophilicity measurement solvatochromic analysis of retention mechanisms for neutral and basic compounds. /. Sep. Sci. 2005, 28, 2350-2362. 

As chronicled by Dearden [21], the association of compound lipophilicity with membrane penetration was first implied by Overton and Meyer more than a century ago. To enhance this understanding, lipophilicity measurements were initially performed using a variety of lipid phases [22], while the comprehensive review by Hansch et al. [23], with extensive data from literature and their own measurements, lent further support to the now accepted wide use of the octanol-water solvent system. 

Lipophilicity appears in several Quantitative Structure-Activity Relationships (QSAR) studies [16], emphasizing its importance. Different in vitro assays have been reported to measure lipophilicity from the classical shake-flask technique that still remains the reference for lipophilicity measurements to more actual methodologies. The first procedure is time-consuming, sensitive to impurities and the measurable log Poct range restricted to -3 to 3 [17]. 

Valko, K., Du, C.M., Bevan, C.D., Reynolds, D.P. and Abraham, M.H. (2000) Rapid-gradient HPLC method for measuring drug interactions with immobilized artificial membrane comparison with other lipophilicity measures. Journal of Pharmaceutical Sciences, 89, 1085-1096. 

Chen, Z. and Weber, S.G. (2007) High-throughput method for lipophilicity measurement. Analytical Chemistry, 79, 1043-1049. 

Pagliara, A., Khamis, E., Trinh, A., Carrupt, P.A., Tsai, R.S. and Testa, B. (1995) Structural properties governing retention mechanisms on RP-HPLC stationary phase used for lipophilicity measurements. Journal of Liquid Chromatography, 18, 1721-1745. 

R., The impact of lipophilicity in drug research a case report on beta-blockers, Mini Rev. Med. Chem. 5, 197-205, 2005 Gocan, S., Cimpan, G., and Comer, J., Lipophilicity measurements by liquid chromatography, Adv. Chromatog. 44, 79-176, 2006. 

Based on the cpo concept, a fast gradient method RP-HPLC has been proposed to determine the chromatographic hydrophobicity index (CHI) as a high-throughput alternative to other lipophilicity measures.Eor this... 

The mobile phase used in the lipophilicity measurements by RP-TLC is usually a binary mixture between an organic solvent and water. The organic solvent can be methanol, acetonitrile, or acetone. The first two can also be used in reversed-phase high-performance liquid chromatography (RP-HPLC) measurements, but... 

Fig.l The relationship between the Rm values and the organic-modifier concentration (mobile phase for RP-TLC lipophilicity measurements. 

Faller, B., Grimm, H.P., Loeuillet-Ritzler, F., Arnold, S. and Briand, X. (2005) High-throughput lipophilicity measurement with immobilized artificial membranes. Journal of Medicinal Chemistry, 48, 2571-2576. 

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