Determination of Drugs in Plasma Samples by High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Therapeutic Drug Monitoring of Schizophrenic Patients.
This work describes the development of a simple, sensitive and selective method based on high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) to determine antipsychotics (olanzapine, quetiapine, clozapine, haloperidol and chlorpromazine) along with antidepressants (mirtazapine, paroxetine, citalopram, sertraline, imipramine, clomipramine and fluoxetine), anticonvulsants (carbamazepine and lamotrigine) and anxiolytics (diazepam and clonazepam) in plasma samples obtained from schizophrenic patients. The samples were prepared by protein precipitation. The target drugs were separated on an XSelect SCH C18 column (100 mm × 2.1 mm × 2.5 µm) within 8.0 min by means of gradient elution. The drugs were then detected on a quadrupole tandem mass spectrometer equipped with an electrospray ionization source, operating in the multiple reactions monitoring mode and in the positive ionization mode. The LC-MS-MS method was linear range from subtherapeutic to toxic concentrations with lower limit of quantification values ranged from 0.2 to 5.0 ng mL(-1), precision with coefficient of variation values lower than 12%, and accuracy ranged from 90 to 108%. The developed method enabled successful analysis of the target drugs in plasma samples obtained from 51 schizophrenic patients. Therapeutic drug monitoring revealed that many of the evaluated schizophrenic patients presented altered plasma concentrations of the analyzed drugs. These altered concentrations resulted from pharmacokinetic interactions among the medications prescribed to treat schizophrenia.
Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
Diego Soares
DS
Domingues
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
Mônia Aparecida Lemos
MA
Pinto
Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
Israel Donizeti
ID
de Souza
Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Jaime Eduardo Cecilio
JE
Hallak
Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
José Alexandre de Souza
JA
Crippa
Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil mariaeqn@ffclrp.usp.br.
Maria Eugênia Costa
ME
Queiroz
D053000:Analytic Sample Preparation Methods; D014151:Anti-Anxiety Agents / Q000097:blood / Q000493:pharmacokinetics; D000927:Anticonvulsants / Q000097:blood* / Q000493:pharmacokinetics; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D011619:Psychotropic Drugs / Q000097:blood* / Q000493:pharmacokinetics; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D011619:Psychotropic Drugs