title: Exhaustive and stable electromembrane extraction of acidic drugs from human plasma.
abstract: The first part of the current work systematically described the screening of different types of organic solvents as the supported liquid membrane (SLM) for electromembrane extraction (EME) of acidic drugs, including different alcohols, ketones, and ethers. Seven acidic drugs with a wide logP range (1.01-4.39) were selected as model substances. For the first time, the EME recovery of acidic drugs and system-current across the SLM with each organic solvent as SLM were investigated and correlated to relevant solvent properties such as viscosity and Kamlet and Taft solvatochromic parameters. Solvents with high hydrogen bonding acidity (α) and dipolarity-polarizability (π*) were found to be successful SLMs, and 1-heptanol was the most efficient candidate, which provided EME recovery in the range of 94-110%. Both hydrogen bonding interactions, dipole-dipole interactions, and hydrophobic interactions were involved in stabilizing the deprotonated acidic analytes (with high hydrogen bonding basicity and high dipole moment) during mass transfer across the SLM. The efficiency of the extraction normally decreased with increasing hydrocarbon chain length of the SLM, which was mainly due to increasing viscosity and decreasing α and π* values. The system-current during EME was found to be dependent on the type and the volume of the SLM. In contact with human plasma, an SLM of pure 1-heptanol was unstable, and to improve stability, 1-heptanol was mixed with 2-nitrophenyl octyl ether (NPOE). With this SLM, exhaustive EME was performed from diluted human plasma, and the recoveries of five out of seven analytes were over 91% after 10min EME. This approach was evaluated using HPLC-UV, and the evaluation data were found to be satisfactory.
authors.affiliation: School of Pharmacy, University of Oslo, PO Box 1068, Blindern, Oslo 0316, Norway; G&T Septech AS, PO Box 33, Ytre Enebakk 1917, Norway. Electronic address: cxhuanglab@icloud.com.
authors.forename: Chuixiu
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, University of Oslo, PO Box 1068, Blindern, Oslo 0316, Norway.
authors.forename: Astrid
authors.initials: A
authors.lastname: Gjelstad
authors.affiliation: School of Pharmacy, University of Oslo, PO Box 1068, Blindern, Oslo 0316, Norway.
authors.forename: Knut Fredrik
authors.initials: KF
authors.lastname: Seip
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen DK-2100, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Jensen
authors.affiliation: School of Pharmacy, University of Oslo, PO Box 1068, Blindern, Oslo 0316, Norway; Department of Pharmacy, Faculty of Health and Medical Sciences, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen DK-2100, Denmark. Electronic address: stig.pedersen-bjergaard@farmasi.uio.no.
authors.forename: Stig
authors.initials: S
authors.lastname: Pedersen-Bjergaard
mesh_terms: D002851:Chromatography, High Pressure Liquid; D055664:Electrochemical Techniques; D004987:Ethers / Q000737:chemistry; D019850:Heptanol / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations / Q000097:blood*; D012997:Solvents / Q000737:chemistry*
chemical_list: C519952:2-nitrophenyl octyl ether; D004987:Ethers; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D012997:Solvents; D019850:Heptanol
keywords: Acidic drugs; Electromembrane extraction (EME); Exhaustive extraction; Human plasma; Organic solvent; System-current