Immobilized artificial membrane chromatography: from medicinal chemistry to environmental sciences

Abstract

<jats:p>&lt;p class="ADMETabstracttext"&gt;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&lt;sub&gt;(IAM)&lt;/sub&gt; or extrapolated log k&lt;sub&gt;w(IAM)&lt;/sub&gt; retention factors, chromatographic hydrophobicity index CHI&lt;sub&gt;(IAM)&lt;/sub&gt; or the polarity parameter Δlog k&lt;sub&gt;w(IAM)&lt;/sub&gt; 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.&lt;/p&gt;</jats:p>

Using membrane–water partition coefficients in a critical membrane burden approach to aid the identification of neutral and ionizable chemicals that induce acute toxicity below narcosis levels

“…[33][34][35][36][37][38][39][40][41][42] The development of silica particles coated with an immobilized articial phospholipid membrane for use in high performance liquid chromatography (IAM-HPLC) [43][44][45][46] has enabled measurements of retention capacity factors (k IAM ) that closely relate to descriptors that are valuable for drug development, toxicokinetic modeling and chemical risk assessment in general. 47 IAM-HPLC provides a cost-effective, high-throughput, consistent approach to experimentally derive indicative D MLW values directly from these k IAM measurements. Using k IAM obtained in (or extrapolated to) fully aqueous eluent (i.e., k 0 IAM ), multiplication with a pre-determined medium/ phospholipid volume ratio of the IAM-column (4 = 18.9 (ref.…”

“…33–42 The development of silica particles coated with an immobilized artificial phospholipid membrane for use in high performance liquid chromatography (IAM-HPLC) 43–46 has enabled measurements of retention capacity factors ( k IAM ) that closely relate to descriptors that are valuable for drug development, toxicokinetic modeling and chemical risk assessment in general. 47…”

Biomimetic chromatography—A novel application of the chromatographic principles

“…As a prerequisite, the compound should bind strongly to phospholipids that manifest by long retention times on IAM columns. IAM chromatography has been applied to estimate toxicological endpoints regarding drug safety, such as phospholipidosis potential or chemical risk hazards, including the bioconcentration factor and toxicity in aquatic organisms 49 . The speed, reproducibility and low analyte consumption suggest that a broader application of IAM chromatography may save time and money in initial drug candidate selection and contribute to a reduced risk hazard of chemicals.…”

Immobilized artificial membrane-chromatographic and computational descriptors in studies of soil-water partition of environmentally relevant compounds

“…The more recent applications of IAM chromatography extend from medicinal to environmental chemistry. Studies of compounds' bioconcentration in aquatic organisms (Tsopelas et al 2017(Tsopelas et al , 2018, ecotoxicity of pesticides (Stergiopoulos et al 2019), and soil-water sorption of herbicides (Hidalgo-Rodríguez et al 2012) prove that IAM chromatography is a source of valuable information in many areas of research. The objective of the present study was to propose useful models of the soil-water partition coefficients normalized to organic carbon (K oc ) using a large group of structurally diverse organic compounds, based their IAM chromatographic and computational descriptors.…”