title: Parallel artificial liquid membrane extraction of new psychoactive substances in plasma and whole blood.
abstract: Parallel artificial liquid membrane extraction (PALME) was combined with ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and the potential for screening of new psychoactive substances (NPS) was investigated for the first time. PALME was performed in 96-well format comprising a donor plate, a supported liquid membrane (SLM), and an acceptor plate. Uncharged NPS were extracted from plasma or whole blood, across an organic SLM, and into an aqueous acceptor solution, facilitated by a pH gradient. MDAI (5,6-methylenedioxy-2-aminoindane), methylone, PFA (para-fluoroamphetamine), mCPP (meta-chlorophenylpiperazine), pentedrone, methoxetamine, MDPV (methylenedioxypyrovalerone), ethylphenidate, 2C-E (2,5-dimethoxy-4-ethylphenethylamine), bromo-dragonfly, and AH-7921 (3,4-dichloro-N-{[1-(dimethylamino)cyclohexyl]methyl}benzamide) were selected as representative NPS. Optimization of operational parameters was necessary as the NPS were novel to PALME, and because PALME was performed from whole blood for the very first time. In the PALME method developed for plasma, NPS were extracted from a 250μL alkalized donor solution consisting of 125μL plasma sample, 115μL 40mM NaOH, and 10μL internal standard. In the PALME method from whole blood, the 250μL alkalized donor solution consisted of 100μL whole blood, 50μL deionized water, 75μL 80mM NaOH, and 25μL internal standard. In both methods, extraction was accomplished across an SLM of 5μL dodecyl acetate with 1% trioctylamine (w/w), and further into an acidic acceptor solution of 50μL 20mM formic acid. The extraction was promoted by agitation at 900rpm and was carried out for 120min. Method validation was performed and the following parameters were considered: linearity, limits of quantification (LOQ), intra- and inter-day precision, accuracy, extraction recoveries, carry-over, and matrix effects. The validation results were in accordance with FDA guidelines.
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316 Oslo, Norway.
authors.forename: Linda
authors.initials: L
authors.lastname: Vårdal
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316 Oslo, Norway.
authors.forename: Hilde-Merete
authors.initials: HM
authors.lastname: Askildsen
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316 Oslo, Norway.
authors.forename: Astrid
authors.initials: A
authors.lastname: Gjelstad
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316 Oslo, Norway; Norwegian Institute of Public Health (NIPH), Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway.
authors.forename: Elisabeth Leere
authors.initials: EL
authors.lastname: Øiestad
authors.affiliation: Norwegian Institute of Public Health (NIPH), Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway.
authors.forename: Hilde Marie Erøy
authors.initials: HM
authors.lastname: Edvardsen
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316 Oslo, Norway; Faculty of Health and Medical Sciences, School of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, 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 / Q000379:methods*; D004867:Equipment Design; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction / Q000295:instrumentation / Q000379:methods*; D008567:Membranes, Artificial; D011619:Psychotropic Drugs / Q000097:blood* / Q000302:isolation & purification*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D008567:Membranes, Artificial; D011619:Psychotropic Drugs
keywords: Liquid-phase microextraction; New psychoactive substances; Parallel artificial liquid membrane extraction; Plasma samples; Whole blood samples