The use of immobilized artificial membrane chromatography to predict bioconcentration of pharmaceutical compounds

Tsopelas, Fotios; Stergiopoulos, Chrysanthos; Tsakanika, Lamprini-Areti; Ochsenkühn-Petropoulou, Maria; Tsantili‐Kakoulidou, Anna

doi:10.1016/j.ecoenv.2017.01.028

Cited by 23 publications

(16 citation statements)

References 35 publications

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“…There is general agreement that IAM retention is governed by lipophilicity, involving hydrophobicity, polarity and the additional factors, of electrostatic interactions in the case of ionizable compounds (e.g. deprotonated acids, protonated bases and zwitterions) with the charged centres of the phospholipids and the consequent formation of ionic bonds [17,21,26,31,34,38]. In such cases, IAM retention may be considered as a border case between passive diffusion and binding as was highlighted by Van Balen et al [42].…”

Section: Relationship Of Iam Retention With Lipophilicity and Other Mmentioning

confidence: 97%

“…According to the literature, not only the IAM.PC.DD2 column but also the IAM.PC.MG column are widely employed in pharmaceutical [15][16][17][18][19][20] and environmental research [21]. The difference between the two columns is in the end-capping of the free (unreacted) propylamino residues, performed either by methylglycolate or decyl/propyl anhydride as described in detail in the literature [6,7,[22][23][24].…”

Section: Types Of Iam Stationary Phases and Their Interrelationmentioning

confidence: 99%

“…In the case of ionizable compounds log k w(IAM) may still correlate better with log P than log D as a result of the partial compensation of ionization via electrostatic interactions [26]. However, the relationship of log k w(IAM) with log D can be considerably improved by introducing the positively (F + ) or negatively charged (F -) molecular fraction of the analytes [17,21,26,31,34] as additional parameters. Positive signs (higher for F + than for F -) are generated, as shown in Eq.…”

Section: Relationship Of Iam Retention With Lipophilicity and Other Mmentioning

confidence: 99%

“…A possible explanation for the stronger electrostatic interactions of cations is the location of the IAM phosphate groups close to the hydrophobic part of phospholipids, in contrast to the choline nitrogen which is more exposed to the solvent effect at the outer terminal of the IAM surface [21,26]. Thus, phosphate anions enhance the partitioning of cations into the IAM stationary phase by attraction forces, while as already commented, repulsive forces may occur with anions [21,26]. However, in the case of very hydrophilic anions, partitioning into the hydrophobic core may not be the determinant factor and attraction by the positively charged choline nitrogen becomes similarly important.…”

Section: Relationship Of Iam Retention With Lipophilicity and Other Mmentioning

confidence: 99%

“…The potential of IAM chromatography to predict bioconcentration of pharmaceutical compounds in aquatic organisms was recently investigated by our group [21]. Since very limited experimental bioconcentration factors (BCF) of pharmaceutical compounds are available, BCF values predicted by EPI Suite Software were used to compile a data set of 125 structurally diverse drugs.…”

Section: The Use Of Iam Chromatography For the Prediction Of Ecotoxicitymentioning

confidence: 99%

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Immobilized artificial membrane chromatography: from medicinal chemistry to environmental sciences

Tsopelas

Stergiopoulos²,

Tsantili‐Kakoulidou³

2018

ADMET DMPK

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Immobilized Artificial Membrane (IAM) chromatography constitutes a valuable tool for medicinal chemists to prioritize drug candidates in early drug development. The retention on IAM stationary phases encodes lipophilicity, electrostatic and other secondary interactions contrary to traditional octanol-water partitioning. An increasing number of publications in recent years have suggested that IAM indices, including isocratic log k(IAM) or extrapolated log kw(IAM) retention factors, chromatographic hydrophobicity index CHI(IAM) or the polarity parameter Δlog kw(IAM) can successfully model the passage of xeniobiotics through biological membranes and barriers and predict pharmacokinetic properties, often in combination with additional descriptors. Examples referring to the modeling of human oral absorption, blood-brain penetration and skin partition are described. More recently, IAM chromatography has been applied to estimate toxicological endpoints in regard to drug safety, such as phospholipidosis potential, or in regard to chemical risk hazards including the bioconcentration factor and aquatic organisms’ toxicity. The promising results in both medicinal chemistry and in environmental science in combination with the speed, reproducibility and low analyte consumption suggest that a broader application of IAM chromatography in the early drug discovery process and in ecotoxicity may save time and money in initial drug candidate selection and will contribute to a reduced risk hazard of chemicals.

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Section: Relationship Of Iam Retention With Lipophilicity and Other Mmentioning

confidence: 97%

Section: Types Of Iam Stationary Phases and Their Interrelationmentioning

confidence: 99%

Section: Relationship Of Iam Retention With Lipophilicity and Other Mmentioning

confidence: 99%

Section: Relationship Of Iam Retention With Lipophilicity and Other Mmentioning

confidence: 99%

Section: The Use Of Iam Chromatography For the Prediction Of Ecotoxicitymentioning

confidence: 99%

See 3 more Smart Citations

Immobilized artificial membrane chromatography: from medicinal chemistry to environmental sciences

Tsopelas

Stergiopoulos²,

Tsantili‐Kakoulidou³

2018

ADMET DMPK

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The QSAR Paradigm to Explore and Predict Aquatic Toxicity

Tsopelas¹,

Tsantili‐Kakoulidou²

2021

Chemometrics and Cheminformatics in Aquatic Toxicology

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Determination of lipid–water partition coefficient of neutral and ionic drugs by liposome electrokinetic chromatography

et al. 2021

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Profiling of lipid–water partition coefficients (KL/W) of drugs is an essential issue during the early stage of drug development. In this study, two liposomes, including 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC) + cholesterol (Chol) (DSPC/Chol liposomes) and soybean lecithin (SPC) + Chol (SPC/Chol liposomes), were prepared for the liposome electrokinetic chromatography (LEKC) analysis, and the logarithm of lipid–water partition coefficients (log KL/W) of neutral and ionic drugs were determined based on an iterative method. The log KL/W values determined by the SPC/Chol or DSPC/Chol liposomes LEKC were linearly fitted, which showed a good fitting coefficient (R2 = 0.89). Furthermore, the linear relationship between the data obtained from LEKC system and octanol–water system, immobilized artificial membrane, Caco‐2 cell model, and software prediction was analyzed, respectively. Results illustrated that DSPC/Chol liposomes or SPC/Chol liposomes had a good linear relationship with Caco‐2 cell model, and R2 was 0.81 and 0.72, respectively. Moreover, the linear free energy relationship analysis suggested that the solute volume, hydrogen bond basicity, and J– were the main descriptors that drove the partition process of solutes in the SPC/Chol or DSPC/Chol LEKC system. In addition, the normalized properties of the SPC/Chol and DSPC/Chol LEKC systems through linear free energy relationship analysis were very close. In short, DSPC/Chol liposomes are more suitable for simulating cell membranes than SPC/Chol liposomes, and the developed LEKC is an effective partitioning model for measuring the log KL/W of drugs.

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The use of immobilized artificial membrane chromatography to predict bioconcentration of pharmaceutical compounds

Cited by 23 publications

References 35 publications

Immobilized artificial membrane chromatography: from medicinal chemistry to environmental sciences

Immobilized artificial membrane chromatography: from medicinal chemistry to environmental sciences

The QSAR Paradigm to Explore and Predict Aquatic Toxicity

Determination of lipid–water partition coefficient of neutral and ionic drugs by liposome electrokinetic chromatography

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