Into the first biomimetic sphingomyelin stationary phase: Suitability in drugs’ biopharmaceutic profiling and block relevance analysis of selectivity

Russo, Giacomo; Ermondi, Giuseppe; Verzele, Dieter; Lynen, Frédéric

doi:10.1016/j.ejps.2020.105585

Cited by 9 publications

(4 citation statements)

References 51 publications

(69 reference statements)

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“…SPH biomimetic stationary phase for investigating putative drug molecules’ blood/brain barrier distribution was published in 2021 23 . A good correlation was found 23 between the new SPH phase named IAM. SPH and the IAM membrane column with phosphatidylcholine, drug discovery (IAM.PC.…”

Section: Introductionmentioning

confidence: 94%

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Biomimetic chromatography—A novel application of the chromatographic principles

Valkó¹

2022

Analytical Science Advances

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Biomimetic chromatography is the name of the High Performance Liquid Chromatography (HPLC) methods that apply stationary phases containing proteins and phospholipids that can mimic the biological environment where drug molecules distribute. The applied mobile phases are aqueous organic with a pH of 7.4 to imitate physiological conditions that would be encountered in the human body. The calibrated retention of molecules on biomimetic stationary phases reveals a compound's affinity to proteins and phospholipids, which can be used to model the biological and environmental fate of molecules. This technology, when standardised, enables the prediction of in vivo partition and distribution behaviour of compounds and aids the selection of the best compounds for further studies to become a drug molecule. Applying biomimetic chromatographic measurements helps reduce the number of animal experiments during the drug discovery process. New biomimetic stationary phases, such as sphingomyelin and phosphatidylethanolamine, widen the application to the modelling of blood-brain barrier distribution and lung tissue binding. Recently, the measured properties have also been used to predict toxicity, such as phospholipidosis and cardiotoxicity. The aquatic toxicity of drugs and pesticides can be predicted using biomimetic chromatographic data. Biomimetic chromatographic separation methods may also be extended in the future to predict protein and receptor binding kinetics. The development of new biomimetic stationary phases and new prediction models will further accelerate the widespread application of this analytical method.

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Section: Introductionmentioning

confidence: 94%

“…The synthesis and analysis of the new IAM. SPH biomimetic stationary phase for investigating putative drug molecules’ blood/brain barrier distribution was published in 2021 23 . A good correlation was found 23 between the new SPH phase named IAM.…”

Section: Introductionmentioning

confidence: 94%

Biomimetic chromatography—A novel application of the chromatographic principles

Valkó¹

2022

Analytical Science Advances

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“…Separation science offers valuable alternatives to animal testing that can provide effectiveness in the drug discovery/drug development pipeline as biomimetic liquid chromatography [8][9][10][11], performed employing stationary phases emulating biological components or using mobile phase ingredients simulating physiological environments. A consistent branch of this is represented by liquid chromatography (LC) conducted on stationary phases based on immobilized artificial membranes (IAM).…”

Section: Introductionmentioning

confidence: 99%

cΔlog kwIAM: can we afford estimation of small molecules’ blood-brain barrier passage based upon in silico phospholipophilicity?

Grumetto

Russo

2021

ADMET DMPK

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56 compounds, whose log BB values were known from the scientific literature, were considered and their phospholipophilicity values were calculated in silico. These values, along with either experimentally determined or calculated lipophilicity values, were used to extract cΔ/Δ’log kwIAM parameters. cΔ/Δ’log kwIAM values were found inversely related to data of blood-brain barrier passage, especially in the < -0.20 log BB range and on the IAM.PC.DD2 phase (r2 = 0.79). In multiple linear regression, satisfactory statistic models (r2 (n-1) = 0.76), based on cD/D’log kwIAM.MG along with other in silico calculated descriptors, were achieved. This method brings the potential to be applied, along with other methodologies, to filter out solutes whose BBB permeation is foreseen to be substandard, thus allowing pharmaceutical companies/research institutes to focus on candidates that are more likely to concentrate in the brain.

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“…Indeed, Quantitative Structure-Property Relationship (QSPR) strategies have been successfully applied to the modelling of chromatographic indexes [17] from a variety of separation modes. Recently we introduced the QSPR/ Partial Least Square (PLS)/Block Relevance (BR) analysis (hereafter named BR analysis), a chemoinformatic tool which affords an interpretation of QSPR models based on a selected pool of descriptors and a PLS algorithm [18][19][20][21][22] . The main readout of BR analysis is a couple of plots in which the main components of the in-termolecular interactions are quantified and output as blocks.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the new CelerisTM Arginine column: Retentive behaviour through a combination of chemometric tools and potential in drug analysis

Russo

Vallaro

Cappelli

et al. 2021

Journal of Chromatography A

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Celeris TM Arginine (ARG) is a mixed-mode stationary phase recently released on the market. To characterize its analytical behavior, the retention factors of a pool ( n = 100, of which 36 neutrals, 26 acids and 38 bases) of pharmaceutically relevant compounds have been measured on this phase over eight percentages (from 10 to 90% v/v) of acetonitrile (MeCN) as organic modifier. The ARG phase exhibited enhanced affinity for the molecules that are in their anionic form at the experimental pH, whilst basic compounds, albeit over a wide range of lipophilicity and pK a values, were on average poorly retained. To dissect the separation mechanism of the ARG phase, the overall analytical retention has been deconvoluted into the individual contributions of intermolecular forces by a QSPR/ Partial Least Square (PLS)/Block Relevance (BR) analysis tool recently developed by us.For the neutrals, the most relevant blocks were found to be Size, describing the interaction due to the dimension of the molecule, and O, representing the solute's hydrogen bond donor properties. The change in sign from positive to negative of the Size block, which occurs between 10% and 20% MeCN, allowed to visually appreciate the switch in the separation mode from reversed phase to normal phase. Some good statistic models for rationalizing the analytical behaviour of neutrals were developed from VS + descriptors. However, their performance in modelling the analytical retention of acids was substandard, probably due to the intrinsic inefficacy of VS + descriptors in handling electric charges. This instance was addressed by a complimentary MLR strategy, which led to successfully model the retention of acids on the ARG column and to shed light into their retention mechanism, which seemed to be substantially driven by electrostatics.

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Into the first biomimetic sphingomyelin stationary phase: Suitability in drugs’ biopharmaceutic profiling and block relevance analysis of selectivity

Cited by 9 publications

References 51 publications

Biomimetic chromatography—A novel application of the chromatographic principles

Biomimetic chromatography—A novel application of the chromatographic principles

cΔlog kwIAM: can we afford estimation of small molecules’ blood-brain barrier passage based upon in silico phospholipophilicity?

Characterization of the new CelerisTM Arginine column: Retentive behaviour through a combination of chemometric tools and potential in drug analysis

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