title: Parallel artificial liquid membrane extraction as an efficient tool for removal of phospholipids from human plasma.
abstract: Generic Parallel Artificial Liquid Membrane Extraction (PALME) methods for non-polar basic and non-polar acidic drugs from human plasma were investigated with respect to phospholipid removal. In both cases, extractions in 96-well format were performed from plasma (125μL), through 4μL organic solvent used as supported liquid membranes (SLMs), and into 50μL aqueous acceptor solutions. The acceptor solutions were subsequently analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using in-source fragmentation and monitoring the m/z 184→184 transition for investigation of phosphatidylcholines (PC), sphingomyelins (SM), and lysophosphatidylcholines (Lyso-PC). In both generic methods, no phospholipids were detected in the acceptor solutions. Thus, PALME appeared to be highly efficient for phospholipid removal. To further support this, qualitative (post-column infusion) and quantitative matrix effects were investigated with fluoxetine, fluvoxamine, and quetiapine as model analytes. No signs of matrix effects were observed. Finally, PALME was evaluated for the aforementioned drug substances, and data were in accordance with European Medicines Agency (EMA) guidelines.
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway.
authors.forename: Kristine Skoglund
authors.initials: KS
authors.lastname: Ask
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway.
authors.forename: Turgay
authors.initials: T
authors.lastname: Bardakci
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway.
authors.forename: Marthe Petrine
authors.initials: MP
authors.lastname: Parmer
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway.
authors.forename: Trine Grønhaug
authors.initials: TG
authors.lastname: Halvorsen
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway; Norwegian Institute of Public Health, Division of Forensic Toxicology and Drug Abuse, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Elisabeth Leere
authors.initials: EL
authors.lastname: Øiestad
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway; School of Pharmaceutical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Stig
authors.initials: S
authors.lastname: Pedersen-Bjergaard
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway. Electronic address: astrid.gjelstad@farmasi.uio.no.
authors.forename: Astrid
authors.initials: A
authors.lastname: Gjelstad
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D005473:Fluoxetine / Q000737:chemistry; D016666:Fluvoxamine / Q000737:chemistry; D006801:Humans; D008244:Lysophosphatidylcholines / Q000737:chemistry; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D010949:Plasma / Q000737:chemistry*; D000069348:Quetiapine Fumarate / Q000737:chemistry; D013109:Sphingomyelins / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D008244:Lysophosphatidylcholines; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D010743:Phospholipids; D013109:Sphingomyelins; D005473:Fluoxetine; D000069348:Quetiapine Fumarate; D016666:Fluvoxamine
keywords: Matrix effects; Membrane extraction; Parallel artificial liquid membrane extraction; Phospholipid removal; Sample preparation