title: Selective solid-phase extraction using molecularly imprinted polymers for analysis of venlafaxine, O-desmethylvenlafaxine, and N-desmethylvenlafaxine in plasma samples by liquid chromatography-tandem mass spectrometry.
abstract: This paper focuses on the development of a novel miniaturized molecularly imprinted solid-phase extraction (MISPE) and ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine venlafaxine (VEN), O-desmethylvenlafaxine (ODV), and N-desmethylvenlafaxine (NDV) in plasma samples. The molecularly imprinted polymer (MIP) was prepared by the precipitation polymerization approach; VEN, metacrylic acid, ethylene glycol dimethacrylate, 2,2-azobisisobutyronitrile, and toluene were used as template, monomer, crosslinker, initiator, and porogen solvent, respectively. MIP and of the non-imprinted control polymer (NIP) sorbents were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. MIP phase presented higher extraction efficiency (MISPE, using plasma samples spiked with VEN) than the NIP phase (84 and 49% recovery rates, respectively). Analysis of other antidepressants with different chemical structures by MISPE-UHPLC-MS/MS attested to the selectivity of the developed MIP. The developed method presented precision assays with coefficients of variation (CV) smaller than 15%; accuracy assays with relative standard error (RSE%) values ranging from -12 to 16%, and linear ranges from 3 to 700ngmL(-1) for VEN, from 5 to 700ngmL(-1) for ODV, and from 3 to 500ngmL(-1) for NDV. The coefficients of determination (r(2)) were higher than 0.995. The lack-of-fit test also attested to the linearity of this method. This method was successfully applied to determine VEN, NDV, and ODV in plasma samples from depressed patients undergoing therapy with VEN.
authors.affiliation: Departamento de Química, Faculdade de Filosofia Ciência e Letras de Ribeirão Preto, Universidade de São Paulo, P.O. Box 14040-901, Ribeirão Preto, SP, Brazil.
authors.forename: Luis Felippe C
authors.initials: LF
authors.lastname: Miranda
authors.affiliation: Departamento de Química, Faculdade de Filosofia Ciência e Letras de Ribeirão Preto, Universidade de São Paulo, P.O. Box 14040-901, Ribeirão Preto, SP, Brazil.
authors.forename: Diego S
authors.initials: DS
authors.lastname: Domingues
authors.affiliation: Departamento de Química, Faculdade de Filosofia Ciência e Letras de Ribeirão Preto, Universidade de São Paulo, P.O. Box 14040-901, Ribeirão Preto, SP, Brazil. Electronic address: mariaeqn@ffclrp.usp.br.
authors.forename: Maria Eugênia C
authors.initials: ME
authors.lastname: Queiroz
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000928:Antidepressive Agents / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003511:Cyclohexanols / Q000097:blood* / Q000378:metabolism; D003863:Depression / Q000097:blood / Q000188:drug therapy; D000069468:Desvenlafaxine Succinate / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008689:Methacrylates / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D054802:Molecular Imprinting; D009570:Nitriles / Q000737:chemistry; D058105:Polymerization; D011108:Polymers / Q000737:chemistry*; D052616:Solid Phase Extraction / Q000379:methods*; D017550:Spectroscopy, Fourier Transform Infrared; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014050:Toluene / Q000737:chemistry; D000069470:Venlafaxine Hydrochloride / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000179:Acrylates; D000928:Antidepressive Agents; D003511:Cyclohexanols; D008689:Methacrylates; D009570:Nitriles; D011108:Polymers; C434332:N-desmethylvenlafaxine; D014050:Toluene; C004919:ethylene dimethacrylate; D000069470:Venlafaxine Hydrochloride; C004526:azobis(isobutyronitrile); C036658:acrylic acid; D000069468:Desvenlafaxine Succinate
keywords: Venlafaxine; molecularly imprinted polymer; plasma samples; ultra-high performance liquid chromatography tandem mass spectrometry