title: Determination of drugs in plasma samples by disposable pipette extraction with C18-BSA phase and liquid chromatography-tandem mass spectrometry.
abstract: This work describes restricted access material (RAM) constituted of porous octadecylsilane particles with the outer surface covered with bovine serum albumin (C18-BSA) as a stationary phase to extract drugs from plasma samples by disposable pipette extraction (DPX) for further analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The C18-BSA phase simultaneously excluded macromolecules by chemical diffusion barrier (BSA network) and enrichment of the interior phase (C18) with drug traces by sorption. The hydrophilic barrier of the C18-BSA allows small molecules (drugs) to permeate through the hydrophobic part (C18), while at the same time it excludes the macromolecules by chemical diffusion barrier (BSA network). Optimization of the DPX variables (sorption equilibration time, exclusion of endogenous compounds, and elution step) improved the sensitivity and selectivity of the method, which presented a linear range from the lower limit of quantification (0.5-20.0ngmL-1) to the upper limit of quantification (32.5-10,500ngmL-1), inter- and intra-assay precision with coefficients of variation (CV) lower than 15%, and relative standard error (RSE) of the accuracy ranging from -12% to 11%. The developed method was successfully used to determine five antipsychotics (olanzapine, quetiapine, clozapine, haloperidol, and chlorpromazine) in combination with seven antidepressants (mirtazapine, paroxetine, citalopram, sertraline, imipramine, clomipramine, and fluoxetine), two anticonvulsants (carbamazepine and lamotrigine), and two anxiolytics (diazepam and clonazepam) in plasma samples from schizophrenic patients for therapeutic drug monitoring.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Café Avenue S/N, Ribeirão Preto, SP 14040903, Brazil.
authors.forename: Mônia Ap Lemos
authors.initials: MAL
authors.lastname: Pinto
authors.affiliation: Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Bandeirantes Avenue 3900, Ribeirão Preto, SP 14040-903, Brazil.
authors.forename: Israel D
authors.initials: ID
authors.lastname: de Souza
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Café Avenue S/N, Ribeirão Preto, SP 14040903, Brazil; Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Bandeirantes Avenue 3900, Ribeirão Preto, SP 14040-903, Brazil. Electronic address: mariaeqn@ffclrp.usp.br.
authors.forename: Maria Eugênia C
authors.initials: MEC
authors.lastname: Queiroz
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000097:blood; D000927:Anticonvulsants / Q000097:blood; D000928:Antidepressive Agents / Q000097:blood; D014150:Antipsychotic Agents / Q000097:blood; D002417:Cattle; D002491:Central Nervous System Agents / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods; D004209:Disposable Equipment; D006801:Humans; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D002491:Central Nervous System Agents; D012710:Serum Albumin, Bovine
keywords: Disposable pipette extraction; Drugs; Plasma samples; Restricted access material; Schizophrenia