High throughput determination log Po/w/pKa/log Do/w of drugs by combination of UHPLC and CE methods

Cabot, Joan M.; Subirats, Xavier; Fuguet, Elisabet; Rosés, Martı́

doi:10.5599/admet.2.2.44

Cited by 5 publications

(4 citation statements)

References 12 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…originally intended for screening purposes, based on the retention of compounds in a reversed-phase column under a fast gradient elution. In the present work CHI measurements were carried out via the UHPLC method as described elsewhere, using acetonitrile as the organic modifier and aqueous solutions of 50 mM ammonium acetate at the desired pH value (3.0, 7.4, and 11.0)[14]. In the case of neutral species, CHI values were converted into a log P o/w lipophilicity scale by means…”

mentioning

confidence: 99%

Lipophilicity of amphoteric and zwitterionic compounds: A comparative study of determination methods

Ràfols

Subirats

Rubio

et al. 2017

Talanta

Self Cite

View full text Add to dashboard Cite

Common drugs intended for action in plasma (antibacterials, antiallergics, diuretics...) often display both acidic and basic behavior, and some of these amphoteric compounds can appear as zwitterions. In such cases, accurate profiling of lipophilicity vs. pH, which plays a fundamental role in drug pharmacokinetics, might be complex. In the present work two common lipophilicity determination methods based on the drug distribution between 1-octanol and aqueous buffer i.e. phase equilibration (shake-flask) and two-phase titration (potentiometry), were compared with a high-throughput lipophilicity index, the Chromatographic Hydrophobicity Index (CHI). The results were also compared with log D pH-profiles calculated by different algorithms from ACD/Labs. Accurate and similar results were obtained for both octanol-water approaches but, due to the lower determination times and the absence of different ion-pairing buffers, potentiometry was shown to be the most convenient method. CHI vs. pH profiles provide rapid and efficient information, which is very convenient for lipophilicity screening purposes, but may differ slightly from shake-flask and potentiometric results.

show abstract

mentioning

confidence: 99%

Lipophilicity of amphoteric and zwitterionic compounds: A comparative study of determination methods

Ràfols

Subirats

Rubio

et al. 2017

Talanta

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thirty‐eight compounds with varying functional groups and size and with published values for P o/w (Table ) were used to determine the effectiveness of these nanodiscs for indirect measurement of P o/w and D pH7.0 . Retention factors ( k ) for these were measured and are reported in Table .…”

Section: Resultsmentioning

confidence: 99%

Phospholipid bilayer affinities and solvation characteristics by electrokinetic chromatography with a nanodisc pseudostationary phase

et al. 2016

View full text Add to dashboard Cite

Phospholipid bilayer nanodiscs composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and synthetic maleic acid-styrene copolymer belts have been introduced as a pseudostationary phase (PSP) in electrokinetic chromatography and demonstrated good performance. The nanodiscs provide a suitable migration range and high theoretical plate counts. Using this nanodisc PSP, the affinity of the bilayer structure for probe solutes was determined and characterized. Good correlation is observed between retention factors and octanol water partition coefficients for particular categories of solutes, but the general correlation is weak primarily because the nanodiscs show stronger affinity than octanol for hydrogen bond donors. This suggests that a more appropriate application of this technology is to measure and characterize interactions between solutes and lipid bilayers directly. Linear solvation energy relationship analysis of the nanodisc-solute interactions in this study demonstrates that the nanodiscs provide a solvation environment with low cohesivity and weak hydrogen bond donating ability, and provide relatively strong hydrogen bond acceptor strength.

show abstract

“…and were used to calculate their log D pH10 values. To simplify the calculations, we used an approach that has been previously used by many groups , where it was assumed that log P i is 3.15 less than the log P . A value of 3.15 is a typical average difference that can vary based on ionic strength and structure of compound.…”

Section: Calculationsmentioning

confidence: 99%

Lipophilicity profiling of anthracycline antibiotics by microemulsion electrokinetic chromatography–effects on cardiotoxicity and endotheliotoxicity

et al. 2019

View full text Add to dashboard Cite

Accurate profiling of the lipophilicity of amphoteric compounds might be complex and laborious. In the present work the lipophilicity of 12 anthracycline antibiotics–four parent drugs: doxorubicin, daunorubicin, epidoxorubicin, and epidaunorubicin and eight novel formamidyne derivatives with attached morpholine, hexamethylenoimine or piperidine rings–was determined based on novel approach using MEEKC. In the second stage, lipophilicity was correlated with anthracycline toxicity towards two cell lines. In rat cardiomyoblast cell line (h9c2) a significant correlation between the logP and toxicity was found. The anthracycline lipophilicity was not correlated with toxicity towards the endothelial hybrid cell line (EAhy.926). In conclusion, the lipophilicity of anthracyclines seems to determine their toxicity towards cardiomyoblasts but not on endothelial cells, suggesting a different mechanism of anthracyclines intercellular transport or extrusion in cardiomyoblast and endothelial cells.

show abstract

High throughput determination log Po/w/pKa/log Do/w of drugs by combination of UHPLC and CE methods

Abstract: In 1997 Valkó et al. developed

Cited by 5 publications

References 12 publications

Lipophilicity of amphoteric and zwitterionic compounds: A comparative study of determination methods

Lipophilicity of amphoteric and zwitterionic compounds: A comparative study of determination methods

Phospholipid bilayer affinities and solvation characteristics by electrokinetic chromatography with a nanodisc pseudostationary phase

Lipophilicity profiling of anthracycline antibiotics by microemulsion electrokinetic chromatography–effects on cardiotoxicity and endotheliotoxicity

Contact Info

Product

Resources

About