PH-Metric logP.4. Comparison of Partition Coefficients Determined by HPLC and Potentiometric Methods to Literature Values

Slater, Bryan; Mccormack, A. J.; Avdeef, Alex; Comer, John

doi:10.1002/jps.2600830918

Cited by 120 publications

(81 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The agreement with the SF method is excellent according to validation studies [103,104]. However, it has limited capacity and cannot be used for compounds with pK a out of the established measurable pH range.…”

Section: Potentiometric Methodsmentioning

confidence: 94%

Physicochemical Profiling in Drug Research and Development

Takács‐Novák¹

2012

Physico-Chemical Methods in Drug Discovery and Development

View full text Add to dashboard Cite

Section: Potentiometric Methodsmentioning

confidence: 94%

Physicochemical Profiling in Drug Research and Development

Takács‐Novák¹

2012

Physico-Chemical Methods in Drug Discovery and Development

View full text Add to dashboard Cite

“…More commonly the base 10 logarithm is quoted, i.e., log (10) D 7.4 . The gold standard technique for determining log D 7.4 is widely accepted to be the shake-flask [20,21] and in modern drug discovery miniaturized and automated shake-flask methods have been developed [22][23][24] Other methods include water plug aspiration and injection, [25] chromatographic retention time, [26] pH-metric, [27] microfluidic liquid-liquid extraction, [28] immobilized artificial membrane affinity, [29] and micellar emulsion electrokinetic chromatography methods [30]. Within AstraZeneca, the majority of log D 7.4 measurements are from variants of the shake-flask method [23,24] followed by variants of the chromatographic retention time method [21].…”

Section: Lipophilicitymentioning

confidence: 99%

Interpreting physicochemical experimental data sets

Colclough

Wenlock

2015

J Comput Aided Mol Des

View full text Add to dashboard Cite

With the wealth of experimental physicochemical data available to chemoinformaticians from the literature, commercial, and company databases an increasing challenge is the interpretation of such datasets. Subtle differences in experimental methodology used to generate these datasets can give rise to variations in physicochemical property values. Such methodology nuances will be apparent to an expert experimentalist but not necessarily to the data analyst and modeller. This paper describes the differences between common methodologies for measuring the four most important physicochemical properties namely aqueous solubility, octan-1-ol/water distribution coefficient, pK(a) and plasma protein binding highlighting key factors that can lead to systematic differences. Insight is given into how to identify datasets suitable for combining.

show abstract

“…The log P value was calculated from HPLC retention times by comparison with 12 reference compounds whose log P values were known from octanol-water partitioning (hydroxyquinone, 0.55 [9]; phenol, 1.49; 4-nitrophenol, 1.91; 2-methylphenol, 1.95; 4-chlorophenol, 2.39; bromobenzene, 2.99; napthalene, 3.37; biphenyl, 4.04; anthracene, 4.45 [10]; benzoic acid, 1.83 [11]; tyrosine, 2.32 [12]; toluene, 2.76 [7]). The retention times (t R ) of antioxidants were determined by a Hewlett Packard 1100 series HPLC system equipped with vacuum degasser, quaternary pump, autosampler, and photodiode-array detector.…”

Section: Measurement Of the Partition Coefficient (Log P)mentioning

confidence: 99%

Lipid peroxidation inhibition capacity assay for antioxidants based on liposomal membranes

Zhang

Stanley

Melton

2006

Mol. Nutr. Food Res.

View full text Add to dashboard Cite

An in vitro antioxidant assay has been developed to better reflect the in vivo conditions of antioxidants interacting with membrane and lipid surfaces. The lipid peroxidation inhibition capacity (LPIC) method measures the ability of both lipophilic and hydrophilic antioxidants to protect a lipophilic fluorescent probe 4, 4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid, incorporated in the membrane, from 2,2'-azobis(2-amidinopropane)hydrochloride generated radicals in the surrounding aqueous solution. Antioxidant activities of test compounds were measured either after they were mixed with preformed liposomes (LPIC(Mixed)) or after they were incorporated into liposomes (LPIC(Inco)) as they were made. The results were analysed to determine how the method of mixing and the structures of the antioxidants influenced their protection of the membrane from free radical attack. The LPIC(Mixed) values were larger than the LPIC(Inco) values for a range of 12 structurally diverse antioxidant compounds. However, there was no linear correlation between the lipophilicities, as measured by their partition coefficient, log P and either LPIC(Inco) or LPIC(Mixed) values. A strong correlation was found between LPIC(Inco) and LPIC(Mixed) values.

show abstract

PH-Metric logP.4. Comparison of Partition Coefficients Determined by HPLC and Potentiometric Methods to Literature Values

Cited by 120 publications

References 11 publications

Physicochemical Profiling in Drug Research and Development

Physicochemical Profiling in Drug Research and Development

Interpreting physicochemical experimental data sets

Lipid peroxidation inhibition capacity assay for antioxidants based on liposomal membranes

Contact Info

Product

Resources

About